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Skin blood flow is commonly determined by laser Doppler flowmetry (LDF). It has been suggested that pathophysiological conditions can be assessed by analysis of specific frequency domains of the LDF signals. We tested whether physiological stimuli that activate myogenic and neurogenic mechanisms would affect relevant portions of the laser Doppler spectrum. LDF sensors were placed on the right forearm of 14 healthy volunteers for myogenic (six females) and 13 for neurogenic challenge (five females). Myogenic responses were tested by positioning the arm ∼50° above/below heart level. Neurogenic responses were tested by immersing the left hand into an ice slurry with and without topical application of local anaesthetic. Short-time Fourier analyses were computed over the range of 0.06 to 0.15 Hz for myogenic and 0.02 to 0.06 Hz for neurogenic. No significant differences in spectral density were observed (P = 0.40) in the myogenic range with arm above (7 ± 54 × 10 -4  dB) and below heart (7 ± 14 × 10 -4  dB). Neurogenic spectral density showed no significant increase from baseline to cold pressor test (0.0017 ± 0.0013 and 0.0038 ± 0.0039 dB; P = 0.087, effect size 0.47). After application of anaesthetic, neurogenic spectral density was unchanged between the baseline and cold pressor test (0.0014 ± 0.0025 and 0.0006 ± 0.0005 dB; P = 0.173). These results suggest that changes in the myogenic and neurogenic spectral density of LDF signals did not fully reflect the skin vascular function activated by pressure manipulation and sympathetic stimulation. Therefore, LDF myogenic and neurogenic spectral density data should be interpreted with caution., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P = 0.011). Resting MSNA was negatively correlated with haemoglobin A 1c in all subjects (R = -0.45, P = 0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P < 0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R = 0.69, P < 0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the topic of this review? Sympathoexcitation in both healthy and hypertensive pregnancies, and concurrent adaptations along the neurovascular cascade. What advances does it highlight? Known and plausible adaptations along the neurovascular cascade which may offset elevated MSNA in normotensive pregnancy while also highlighting knowledge gaps regarding understudied pathways., Abstract: The progression from conception through to the postpartum period represents an extraordinary period of physiological adaptation in the mother to support the growth and development of the fetus. Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and sympathetic nerve activity, yet normal or reduced blood pressure; it represents a unique period of apparent healthy sympathetic hyperactivity. However, how this normal blood pressure is achieved in the face of sympathoexcitation, and the mechanisms responsible for this increased activity are unclear. Importantly, sympathetic activation has been implicated in hypertensive pregnancy disorders - the leading causes of maternal-fetal morbidity and mortality in the developed world. An understudied link between pregnancy and the development of maternal hypertension may lie in the sympathetic nervous system regulation of blood pressure. This brief review presents the latest data on sympathoexcitation in both healthy and hypertensive pregnancies, and concurrent adaptations along the neurovascular cascade., (© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the topic of this review? We review barosensory vessel mechanics and their role in blood pressure regulation across the lifespan. What advances does it highlight? In young normotensive men, aortic unloading mechanics contribute to the resting operating point of the vascular sympathetic baroreflex; however, with advancing age, this contribution is removed. This suggests that barosensory vessel unloading mechanics are not driving the well-documented age-related increase in resting muscle sympathetic nerve activity., Abstract: An age-associated increase in arterial blood pressure is evident for apparently healthy humans. This is frequently attributed to stiffening of the central arteries and a concurrent increase in sympathetic outflow, potentially mediated by a reduced ability of the baroreceptive vessels to distend. This is supported, in part, by a reduced mechanical component of the vascular sympathetic baroreflex (i.e., a reduction in distension for a given pressure). Previous characterization of the mechanical component has assessed only carotid artery distension; however, evidence suggests that both the aortic and carotid baroreflexes are integral to blood pressure regulation. In addition, given that baroreceptors are located in the vessel wall, the change in wall tension, comprising diameter, pressure and vessel wall thickness, and the mechanics of this change might provide a better index of the baroreceptor stimulus than the previous method used to characterize the mechanical component that relies on diameter alone. This brief review summarizes the data using this new method of assessing barosensory vessel mechanics and their influence on the vascular sympathetic baroreflex across the lifespan., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings What is the topic of this review? Over the past decade, our team has investigated interindividual variability in human blood pressure regulation., What advances does it highlight? In men, we have found a tight relationship between indices of sympathetic activity and vascular resistance across the age span. This relationship is absent in young women but seen in postmenopausal women. These sex and age differences in vascular resistance are largely a result of changes in the balance of vasodilating and vasoconstricting adrenergic receptor tone. When these changes are considered along with cardiac output, a coherent picture is beginning to emerge of why blood pressure rises more with age in women than men., Arterial pressure is a key regulated variable in the cardiovascular system with important health implications. Over the last 12 years, we have used physiological measurements, including muscle sympathetic nerve activity (MSNA), to explore the balance among mean arterial blood pressure, cardiac output and total peripheral resistance (TPR) in normotensive humans. We have shown that these determinants of blood pressure can vary widely in different subjects and how they vary depends on sex and age. In young men, there is a direct relationship between MSNA and TPR but no relationship with blood pressure. This is because cardiac output is proportionally lower in those with high MSNA and TPR. In contrast, in young women there is no relationship between MSNA and TPR (or cardiac output); this is because β-adrenergic vasodilator mechanisms offset α-adrenergic vasoconstriction. Thus, blood pressure is unrelated to MSNA in young women. In older women, β-adrenergic vasodilator mechanisms are diminished, and a direct relationship between MSNA and TPR is seen. In older men, the relationships among these variables are less clear cut, perhaps owing to age-related alterations in endothelial function. With ageing, the relationship between MSNA and blood pressure becomes positive, more so in women than in men. The finding that the physiological control of blood pressure is so different in men and women and that it varies with age suggests that future studies of mechanisms of hypertension will reveal corresponding differences among groups. [ABSTRACT FROM AUTHOR]

New Findings What is the topic of this review? This review summarizes sex-dependent differences in the sympathetic responses to chemoreflex activation, with a focus on the role of circulating sex hormones on the sympathetic outcomes., What advances does it highlight? The importance of circulating sex hormones for the regulation of sympathetic nerve activity in humans has only recently begun to be elucidated, and few studies have examined this effect during chemoreflex regulation. We review recent studies indicating that changes in circulating sex hormones are associated with alterations to chemoreflex-driven increases in sympathetic activity and highlight those areas which require further study., Sex-dependent differences in baseline sympathetic nerve activity are established, but little information exists on the influence of sex on sympathetic activation during chemoreflex stimulation. In this article, we review the evidence for the effect of sex on chemoreflex-driven increases in sympathetic nerve activity. We also review recent studies which indicate that changes in circulating sex hormones, as initiated by the menstrual cycle and hormonal contraceptive use, elicit notable changes in the muscle sympathetic activation during chemoreflex stimulation. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? The cardiopulmonary baroreflex inhibits adjustment of sympathetic vasomotor outflow during mild-intensity dynamic exercise. However, it is unclear how suppression of sympathetic vasomotor outflow by the cardiopulmonary baroreflex is modulated by a powerful sympatho-excitatory drive from the exercise pressor reflex, central command and/or the arterial chemoreflex., What is the main finding and its importance? Hypoxia-induced heightened sympathetic nerve activity during dynamic exercise attenuated cardiopulmonary baroreflex control of sympathetic vasomotor outflow. This could facilitate the redistribution of blood flow to the active muscles by sympathetically mediated vasoconstriction of inactive muscles., Muscle sympathetic nerve activity (MSNA) does not increase during mild-intensity dynamic leg exercise in normoxic conditions, despite activation of central command and the exercise pressor reflex. Suppression of MSNA could be caused by muscle pump-induced loading of cardiopulmonary baroreceptors. In contrast, MSNA increases during mild dynamic leg exercise in hypoxic conditions. We hypothesized that hypoxic exercise, which induces a powerful sympatho-excitatory drive from the exercise pressor reflex, central command and/or arterial chemoreflex, attenuates cardiopulmonary reflex control of sympathetic vasomotor outflow. To test this hypothesis, MSNA was recorded during leg cycling in hypoxic conditions and with increased central blood volume by increasing the pedalling frequency to change the cardiopulmonary baroreflex. Subjects performed two leg cycle exercises at different pedal cadences of 60 and 80 r.p.m. (60EX and 80EX trials, respectively) in two (haemodynamic and MSNA) measurement conditions while breathing a hypoxic gas mixture (inspired oxygen fraction = 0.12). Thoracic impedance, stroke volume and cardiac output were measured non-invasively using impedance cardiography. During the MSNA test, MSNA was recorded via microneurography at the right median nerve at the elbow. Changes in thoracic impedance, stroke volume and cardiac output during the 80EX trial were greater than those during the 60EX trial. The MSNA burst frequency during hypoxic exercise in the 80EX trial (39 ± 4 bursts min−1) did not differ from that during the 60EX trial (39 ± 3 bursts min−1). These results suggest that the cardiopulmonary baroreflex of sympathetic vasomotor outflow during dynamic exercise is modulated by heightened hypoxia-induced sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia?, What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea., This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg−1 of N-AC ( n = 16) or vehicle placebo ( n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity ( n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo ( P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo ( P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance ( P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? The central question of this study was to investigate the interaction of mild exposures to O2 and CO2 on chemoreflex control of SNA and the modulation of lung volume and respiratory phase on this interaction., What is the main finding and its importance? We demonstrate that the synergistic interaction of oxygen- and carbon dioxide-chemosensitive control of the sympathetic nervous system with hypoxia and hypercapnia exists at very mild excitatory stimuli, is significantly overridden by lung inflation and does not extend to inhibitory modulation by hypocapnia in healthy subjects. These findings demonstrate the important inhibitory modulation of sympathetic nerve activity by lung inflation mechanisms in healthy individuals even in the presence of strong sympathoexcitatory stimuli., We hypothesized that simultaneous stimulation of O2- and CO2-sensitive chemoreflexes produces synergistic activation of the sympathetic nervous system and that this effect would be most apparent at low lung volume (expiratory) phases of respiration. Each subject ( n = 11) breathed 16 gas mixtures in random order: a 4 × 4 matrix of normoxic to hypoxic (8, 12, 16 and 21% O2) combined with normocapnic to hypercapnic gases (0, 2, 4 and 6% CO2). Tidal volume, arterial pressure, heart rate and muscle sympathetic nerve activity (MSNA) were measured continuously before and while breathing each gas mixture for 2 min. Changes in MSNA were determined for each gas mixture. The MSNA was subdivided into low and high lung volume and respiratory phases to investigate further modulation by components of normal respiratory phase. Both hypoxia and hypercapnia increased mean MSNA independently. Mean and low lung volume MSNA increased exponentially with increasing levels of combined hypoxia and hypercapnia and resulted in a significant interaction ( P < 0.01). In contrast, MSNA during the high lung volume phase of respiration never increased significantly ( P > 0.4). Similar but less pronounced effects were found for expiratory and inspiratory phases of respiration. These effects created marked respiratory periodicity in MSNA at higher levels of combined hypoxia and hypercapnia. Finally, the response to hypoxia was not affected by hypocapnia, suggesting that the interaction occurs only during excitatory chemosensitive stimuli. These data indicate that hypoxia and hypercapnia interact to elicit synergistic sympathoexcitation and that withdrawal of sympathoinhibitory effects of lung inflation exaggerates this chemoreflex interaction. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? What is the effect of chronic intermittent hypoxia (a neurogenic model of hypertension that also induces active expiration) on intrinsic electrophysiological properties of rostral ventrolateral medulla presympathetic and putative expiratory neurons recorded in brainstem slices of juvenile rats (postnatal day 35)?, What is the main finding and its importance? Presympathetic neurons and phrenic nucleus-projecting neurons of rostral ventrolateral medulla present characteristics of intrinsic pacemakers, and chronic intermittent hypoxia produces no changes in their intrinsic electrophysiological properties., The presympathetic neurons in the rostral ventrolateral medulla (RVLM) are considered to be the source of the sympathetic activity, and there is experimental evidence that these cells present intrinsic autodepolarization. There is also evidence that an important respiratory neuronal population located in the RVLM/Bötzinger complex (BötC) corresponds to augmenting expiratory neurons (aug-E), which send projections to the phrenic nucleus in the spinal cord. However, the pacemaker activity of presympathetic neurons and the intrinsic properties of aug-E neurons had not been evaluated in brainstem slices of juvenile rats (postnatal day 35). Chronic intermittent hypoxia (CIH) is a sympathetic-mediated hypertension model, which seems to produce an associated increase in the activity of aug-E neurons. In this study, we evaluated the effects of CIH on the intrinsic properties of RVLM/BötC presympathetic and phrenic nucleus-projecting neurons (aug-E) in brainstem slices of juvenile rats (postnatal day 35). We observed that all presympathetic neurons presented spontaneous action potential firing ( n = 18), which was not abolished by ionotropic receptor antagonism. In addition, exposure to 10 days of CIH produced no changes in their intrinsic passive properties, firing pattern or excitability. Most aug-E neurons presented spontaneous firing in control conditions (13 of 15 neurons), and this characteristic was preserved after blocking fast synaptic transmission (12 of 15 neurons), clearly demonstrating their intrinsic pacemaker activity. Chronic intermittent hypoxia also produced no changes in intrinsic passive properties, frequency and pattern of discharge or excitability of the aug-E neurons. The present study shows that: (i) it is possible to record the electrophysiological properties of RVLM/BötC presympathetic and aug-E neurons in brainstem slices from juvenile rats; (ii) these neurons present characteristics of intrinsic pacemakers; and (iii) their intrinsic properties were not altered by chronic intermittent hypoxia. [ABSTRACT FROM AUTHOR]

New Findings What is the topic of this review? Reports that bilateral renal denervation in resistant hypertensive patients results in a long-lasting reduction in blood pressure raise the question of the underlying mechanisms involved and how they may be deranged in pathophysiological states of hypertension and renal failure., What advances does it highlight? The renal sensory afferent nerves and efferent sympathetic nerves work together to exert an important control over extracellular fluid volume, hence the level at which blood pressure is set. This article emphasizes that both the afferent and the efferent renal innervation may contribute to the neural dysregulation of the kidney that occurs in chronic renal disease and resistant hypertension., Autonomic control is central to cardiovascular homeostasis, and this is exerted not only at the level of the heart and blood vessels but also at the kidney. At the kidney, the sympathetic neural regulation of renin release and fluid reabsorption may influence fluid balance and, in the longer term, the level at which blood pressure is set. The role of the renal innervation in the regulation of blood pressure has received renewed attention over the past few years, following the reports that bilateral renal denervation of resistant hypertensive patients resulted in a marked reduction in blood pressure, which has been maintained for several years. Such has been the interest that this approach of renal denervation is being applied in other patient groups with diabetes, obesity and renal failure, with the hope that there may be a sustained reduction in blood pressure as well as the amelioration of some aspects of the metabolic syndrome. However, the factors that come into play to cause the rise in blood pressure in these patient groups, particularly the resistant hypertensive patients, are far from clear. Moreover, the mechanisms leading to the fall in blood pressure following renal denervation of resistant hypertensive patients currently elude our understanding and is therefore an area that requires much more investigation to enhance our insight. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? The functional relationships between central amygdala neuronal activity (CeANA) and sympathetic nerve activity in daily activities remain unclear. We aimed to measure CeANA, renal and lumbar sympathetic nerve activity (RSNA and LSNA, respectively), heart rate (HR) and arterial pressure simultaneously in freely moving rats. What is the main finding and its importance? The CeANA was significantly related to RSNA and LSNA and HR in a behavioural state-dependent and regionally different manner; meanwhile, CeANA was tightly associated with RSNA and HR across all behavioural states. Thus, it is likely that the amygdala is a component of neural networks generating regional differences in RSNA and LSNA., Abstract: The central amygdala (CeA) is involved in generating diverse changes in sympathetic nerve activity (SNA) in response to changes in daily behavioural states. However, the functional relationships between CeA neuronal activity (CeANA) and SNA in daily activities are still unclear. In the present study, we developed a method for simultaneous and continuous measurement of CeANA and SNA in freely moving rats. Wistar rats were chronically instrumented with multiple electrodes (100-μm-thick stainless-steel wire) for the measurement of CeANA, renal SNA (RSNA) and lumbar SNA (LSNA), and electroencephalogram, EMG and ECG electrodes, in addition to catheters for measurement of arterial pressure (AP). During the transition from non-rapid eye movement sleep to quiet wakefulness, moving and grooming states, a significant linear relationship was observed between CeANA and RSNA (P < 0.0001), between CeANA and LSNA (P = 0.0309), between CeANA and heart rate (HR) (P = 0.0123) and between CeANA and EMG (P = 0.0089), but no significant correlation was observed between CeANA and AP (P = 0.5139). During rapid eye movement sleep, the relationships between CeANA and RSNA, LSNA, HR, AP and EMG deviated from the previously observed linear relationships, but the time course of RSNA and HR changes was the mirror image of that of CeANA, whereas the time course of changes in LSNA and AP was not related to that of CeANA. In conclusion, CeANA was related to RSNA, LSNA and HR in a behavioural state-dependent and regionally different manner, and CeANA was tightly associated with RSNA and HR across all behavioural states., (© 2022 The Authors. Experimental Physiology © 2022 The Physiological Society.)

New Findings: What is the central question of this study? Sympathetic vasomotor outflow is reduced during low-intensity dynamic leg exercise in younger individuals: does ageing influence the sympathoinhibitory effect during low-intensity leg cycling? What is the main finding and its importance? Muscle sympathetic nerve activity during low-intensity cycling decreased in older males, as seen in young males. It is possible that cardiopulmonary baroreflex-mediated inhibition of sympathetic vasomotor outflow during dynamic leg exercise is preserved in healthy older males., Abstract: Muscle sympathetic nerve activity (MSNA) is reduced during low-intensity dynamic leg exercise in young males. It is suggested that this inhibition is mediated by loading of the cardiopulmonary baroreceptors. The purpose of this study was to clarify the impact of age on MSNA during dynamic leg exercise. Nine younger males (YM, mean ± SD, 20 ± 1 years) and nine older males (OM, 72 ± 3 years) completed the study. The subjects performed two 4-min cycling exercises at 10% of their heart rate reserve using a cycle ergometer in a semirecumbent position (MSNA and estimated central venous pressure (eCVP) trials). MSNA was recorded via microneurography of the left radial nerve. The CVP was estimated based on peripheral venous pressure, which was monitored using a cannula in the right large antecubital vein. The magnitude of the increase in mean arterial blood pressure during leg cycling was larger in OM (+9.3 ± 5.5 mmHg) compared with YM (+2.8 ± 4.7 mmHg). MSNA burst frequency was decreased during cycling in both YM (-8.1 ± 3.8 bursts/min) and OM (-10.6 ± 3.3 bursts/min), but no significant difference was found between the two groups. The eCVP increased during exercise in both groups, and there was no difference in the changes in eCVP between YM (+1.1 ± 0.4 mmHg) and OM (+1.2 ± 0.7 mmHg). These data indicate that inhibition of sympathetic vasomotor outflow during low-intensity cycling appears in OM as seen in YM. It is possible that the muscle pump-induced loading of the cardiopulmonary baroreflex is preserved during cycling in healthy older males., (© 2022 The Authors. Experimental Physiology © 2022 The Physiological Society.)

New Findings: What is the central question of this study? What is the role of β- and α-adrenergic receptors in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans? What is the main finding and its importance? β-Adrenergic receptor, but not α-adrenergic receptor, blockade significantly blunted the increases in coronary blood velocity observed during handgrip. Coronary blood velocity was unchanged from baseline during isolated muscle metaboreflex activation. This highlights the important role of β-adrenergic receptors in the coronary circulation during handgrip in humans, and the more limited involvement of the α-adrenergic receptors., Abstract: We sought to investigate the role of β- and α-adrenergic receptors in coronary circulation during static handgrip exercise and isolated muscle metaboreflex activation in humans. Seventeen healthy young men underwent two experimental sessions, consisting of 3 min of static handgrip exercise at a target force of 40% maximum voluntary force (not achieved for the full 3 min), and 3 min of metaboreflex activation (post-exercise ischaemia) in two conditions: (1) control and β-blockade (oral propranolol), and (2) control and α-blockade (oral prazosin). In both sessions, coronary blood velocity (CBV, echocardiography) was increased during handgrip (Δ8.0 ± 7.4 cm s -1 ) but unchanged with metaboreflex activation (Δ2.5 ± 3.2 cm s -1 ) under control conditions. β-Blockade abolished the increase in CBV during handgrip, while CBV was unchanged from control with α-blockade. Cardiac work, estimated from rate pressure product (RPP; systolic blood pressure multiplied by heart rate), increased during handgrip and metaboreflex in control conditions in both sessions. β-Blockade reduced RPP responses to handgrip and metaboreflex, whereas α-blockade increased RPP, but the responses to handgrip and metaboreflex were unchanged. CBV and RPP were only significantly correlated during handgrip under control (r = 0.71, P < 0.01) and β-blockade (r = 0.54, P = 0.03) conditions, and the slope of this relationship was unaltered with β-blockade. Collectively, these findings indicate that β-adrenergic receptors play the primary role to the increase of coronary circulation during handgrip exercise, but CBV is unchanged with metaboreflex activation, while α-adrenergic receptor stimulation seems to exert no effect in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

New Findings: What is the central question of this study? Is the arterial baroreflex involved in causing patterned, region-specific changes in sympathetic nerve activity during freezing behaviour in conscious rats? What is the main finding and its importance? Freezing behaviour is accompanied by differential shifts in the baroreflex control of renal and lumbar sympathetic nerve activity and heart rate. It is noteworthy that baroreflex pathways may be discretely separated, allowing differential modification of baroreflex curves that may generate differential changes in sympathetic nerve activity during freezing behaviour., Abstract: The present study was designed to test whether the baroreflex stimulus-response curves for renal sympathetic nerve activity (RSNA), lumbar sympathetic nerve activity (LSNA) and heart rate (HR) were shifted in a regionally specific manner during freezing behaviour in conscious rats. Male Wistar rats were chronically instrumented with electrodes and arterial and venous catheters for measurement of RSNA, LSNA and electrocardiogram. After a 60-min control period, freezing behaviour in conscious rats was induced by exposure to loud white noise (90 dB) for 10 min. The baroreflex curves for RSNA, LSNA and HR were generated by changing systemic arterial pressure using rapid intravenous infusions of vasoactive drugs and then fitted to an inverse sigmoid function curve. During the freezing behaviour, the baroreflex curve for RSNA was expanded upward with a significant (P < 0.001) increase (by 153% compared with the control level) in the upper plateau (maximum capacity of RSNA drive), whereas the baroreflex curve for LSNA remained unchanged. Conversely, the baroreflex curve for HR was shifted leftward with a significant (P = 0.004) decrease (by 11 mmHg relative to the control level) in the midpoint pressure. Our results indicate that baroreflex curve shifts for RSNA, LSNA and HR occur in a regionally specific manner during freezing behaviour. This indicates that baroreflex pathways may be discretely separated, allowing differential modification of baroreflex curves that may generate differential changes in sympathetic nerve activity during freezing behaviour., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

New Findings: What is the central question of this study? Sympathetically mediated vasoconstriction is preserved during hypoxaemia in humans, but our understanding of vascular control comes from predominantly male cohorts. We tested the hypothesis that young women attenuate sympathetically mediated vasoconstriction during steady-state hypoxaemia, whereas men do not? What is the main finding and its importance? Sympathetically mediated vasoconstriction is preserved or even enhanced during steady-state hypoxia in young men, and the peripheral vascular response to sympathetic activation during hypoxaemia is attenuated in young women. These data advance our understanding of sex-related differences in hypoxic vascular control., Abstract: Activation of the sympathetic nervous system causes vasoconstriction and a reduction in peripheral blood flow. Sympathetically mediated vasoconstriction may be attenuated during systemic hypoxia to maintain oxygen delivery; however, in predominantly male participants sympathetically mediated vasoconstriction is preserved or even enhanced during hypoxaemia. Given the potential for sex-specific differences in hypoxic vascular control, prior results are limited in application. We tested the hypothesis that young women attenuate sympathetically mediated vasoconstriction during steady-state hypoxaemia, whereas men do not. Healthy young men (n = 13, 25 ± 4 years) and women (n = 11, 24 ± 4 years) completed two trials consisting of a 2-min cold pressor test (CPT, a well-established sympathoexcitatory stimulus) during baseline normoxia and steady-state hypoxaemia. Beat-to-beat blood pressure (finger photoplethysmography) and forearm blood flow (venous occlusion plethysmography) were measured continuously. Total and forearm vascular conductance (TVC and FVC, respectfully) were calculated. A change (Δ) in TVC and FVC from steady-state during the last 1 min of CPT was calculated and differences between normoxia and systemic hypoxia were assessed. In men, the reduction in TVC during CPT was greater during hypoxia compared to normoxia (ΔTVC, P = 0.02), whereas ΔTVC did not differ between conditions in women (P = 0.49). In men, ΔFVC did not differ between normoxia and hypoxia (P = 0.92). In women, the reduction in FVC during CPT was attenuated during hypoxia (ΔFVC, P < 0.01). We confirm sympathetically mediated vasoconstriction is preserved or enhanced during hypoxaemia in young men, whereas peripheral vascular responsiveness to sympathetic activation during hypoxaemia is attenuated in young women. The results advance our understanding of sex-related differences in hypoxic vascular control., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

New Findings: What is the central question of this study? Do mice submitted to sustained hypoxia present autonomic and respiratory changes similarly to rats? What is the main finding and its importance? Arterial pressure in the normal range, reduced baseline heart rate and tachypnoea were observed in behaving sustained hypoxia mice. Recordings in the in situ preparation of mice submitted to sustained hypoxia show an increase in cervical vagus nerve activity and a simultaneous reduction in thoracic sympathetic nerve activity correlated with changes in the respiratory cycle. Therefore, mice are an important model for studies on the modulation of sympathetic activity to the cardiovascular system and the vagus innervation of the upper airways due to changes in the respiratory network induced by sustained hypoxia., Abstract: Short-term sustained hypoxia (SH) in rats induces sympathetic overactivity and hypertension due to changes in sympathetic-respiratory coupling. However, there are no consistent data about the effect of SH on mice due to the different protocols of hypoxia and difficulties associated with the handling of these rodents under different experimental conditions. In situ recordings of autonomic and respiratory nerves in SH mice have not been performed yet. Herein, we evaluated the effects of SH ( F i O 2  = 0.1 for 24 h) on baseline mean arterial pressure (MAP), heart rate (HR), respiratory frequency (f R ) and responses to chemoreflex activation in behaving SH mice. A characterization of changes in cervical vagus (cVN), thoracic sympathetic (tSN), phrenic (PN) and abdominal (AbN) nerves in SH mice using the in situ working heart-brainstem preparation was also performed. SH mice presented normal MAP, significant reduction in baseline HR, increase in baseline f R , as well as increase in the magnitude of bradycardic response to chemoreflex activation. In in situ preparations, SH mice presented a reduction in PN discharge frequency, and increases in the time of expiration and incidence of late-expiratory bursts in AbN activity. Nerve recordings also indicated a significant increase in cVN activity and a significant reduction in tSN activity during expiration in SH mice. These findings make SH mice an important experimental model for better understanding how changes in the respiratory network may impact on the modulation of vagal control to the upper airways, as well as in the sympathetic activity to the cardiovascular system., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

New Findings: What is the topic of this review? This manuscript provides a review of the current understanding of the role of the sympathetic nervous system in regulation of bone marrow-derived immune cells and the effect that the infiltrating bone marrow cells may have on perpetuation of the sympathetic over-activation in hypertension. What advances does it highlight? We highlight the recent advances in understanding of the neuroimmune interactions both peripherally and centrally as they relate to blood pressure control., Abstract: The sympathetic nervous system (SNS) plays a crucial role in maintaining physiological homeostasis, in part by regulating, integrating and orchestrating processes between many physiological systems, including the immune system. Sympathetic nerves innervate all primary and secondary immune organs, and all cells of the immune system express β-adrenoreceptors. In turn, immune cells can produce cytokines, chemokines and neurotransmitters capable of modulating neuronal activity and, ultimately, SNS activity. Thus, the essential role of the SNS in the regulation of innate and adaptive immune functions is mediated, in part, via β-adrenoreceptor-induced activation of bone marrow cells by noradrenaline. Interestingly, both central and systemic inflammation are well-established hallmarks of hypertension and its co-morbidities, including an inflammatory process involving the transmigration and infiltration of immune cells into tissues. We propose that physiological states that prolong β-adrenoreceptor activation in bone marrow can disrupt neuroimmune homeostasis and impair communication between the immune system and SNS, leading to immune dysregulation, which, in turn, is sustained via a central mechanism involving neuroinflammation., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the central question of this study? We sought to investigate whether young adults reporting low sleep quality possessed lower vascular function and altered autonomic nervous system modulation when compared with young adults reporting high sleep quality. What is the main finding and its importance? The study revealed that in young adults reporting low sleep quality, neither vascular nor autonomic function was significantly different when compared with young adults reporting high sleep quality. These findings suggest that young adults are either not substantially impacted by or can adequately adapt to the negative consequences commonly associated with poor sleep., Abstract: The aim of the study was to investigate whether young adults reporting low sleep quality also possessed lower vascular function, potentially stemming from altered autonomic nervous system modulation, when compared with young adults reporting high sleep quality. Thirty-one healthy young adults (age 24 ± 4 years) underwent a 7 night sleep assessment (Actigraph GT3X accelerometer). After the sleep assessment, subjects meeting specific criteria were separated into high (HSE; ≥85%; n = 11; eight men and three women) and low (LSE; <80%; n = 11; nine men and two women) sleep efficiency groups. Peripheral vascular function was assessed in the upper and lower limb, using the flow-mediated dilatation technique in the arm (brachial artery) and leg (superficial femoral artery). Heart rate variability was evaluated during 5 min of rest and used frequency parameters reflective of parasympathetic and/or sympathetic nervous system modulation (high- and low-frequency parameters). By experimental design, significant differences in sleep quality between groups were reported, with the LSE group exhibiting a longer time awake after sleep onset, higher number of awakenings and longer average time per awakening when compared with the HSE group. Despite these differences in sleep quality, no significant differences in upper and lower limb vascular function and heart rate variability measures were revealed when comparing the LSE and HSE groups. Additionally, in all subjects (n = 31), no correlations between sleep efficiency and vascular function/autonomic modulation were revealed. This study revealed that low sleep quality does not impact upper or lower limb vascular function or autonomic nervous system modulation in young adults., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the central question of this study? Is purinergic signalling in the pial vessels involved in the control of vascular tone in the ventral surface of the brainstem, affecting high blood pressure and sympathetic overactivity in spontaneously hypertensive rats? What is the main finding and its importance? The regulation of vascular tone in the ventral surface of the brainstem is tailored to support neuronal functions, arterial pressure and sympathetic activity. This adds one more piece in the complex puzzle to understand the central mechanisms underlying the genesis of hypertension., Abstract: Evidence suggests the rostral ventrolateral medulla (RVLM) region is chronically hypoperfused and hypoxic in spontaneously hypertensive rats (SHR), which can facilitate ATP release throughout the brainstem. Thus, we hypothesized that purinergic signalling plays a key role in the increased vascular tone in the RVLM region, which in turn could be responsible for the high sympathetic tone and blood pressure in the SHR. The application of an antagonist of P2 receptors, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (10 µm), or of P2Y1a receptors, MRS2179 (100 µm), on the surface of RVLM pial vessels of SHR produced an increase in the diameter of blood vessels (PPADS: 31 ± 1.4 µm or MRS2179: 32 ± 0.78 µm vs. saline: 27 ± 1.2 µm), an effect not observed in normotensive Wistar rats. In addition, the antagonism of P2 receptors was able to evoke a significant decrease in the arterial pressure, heart rate and splanchnic nerve activity in SHR, but not in Wistar rats. Our data show that SHR have higher vascular tone of pial vessels in the RVLM region when compared to the normotensive Wistar rats, a mechanism that relies on purinergic signalling through P2 receptors, suggesting a possible association with higher activity of sympathoexcitatory neurones, and sustained increases in blood pressure., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

New Findings: What is the central question of the study? We have previously shown that sinusoidal galvanic vestibular stimulation induces greater modulation of skin sympathetic nerve activity, but not muscle sympathetic nerve activity, in participants who report nausea during simulated motion, but the effects on skin blood flow and blood pressure are unknown. What is the main finding and its importance? During vestibular stimulation, nausea was associated with a greater increase in skin blood flow and a progressive reduction in skin sympathetic nerve activity, but no changes in muscle sympathetic nerve activity. This emphasizes the differential changes in sympathetic outflow to different tissues during nausea., Abstract: We tested the hypothesis that galvanic vestibular stimulation, which produces illusions of side-to-side swaying, causes a greater reduction in skin blood flow in participants who report stimulation-induced nausea. A retrospective analysis was performed on data obtained in 30 participants. Bipolar sinusoidal galvanic vestibular stimulation (sGVS) was applied across the mastoid processes (±2 mA, 0.08 Hz) for 21 min. ECG, continuous blood pressure, respiration and skin blood flow were recorded. Muscle sympathetic nerve activity was recorded in 17 participants and skin sympathetic nerve activity in 12. Ten participants reported motion sickness, whereas 20 did not. Both groups showed an initial reduction in skin (finger) blood flow during sGVS, followed by a sustained increase and a subsequent return towards baseline levels throughout the stimulation; the increase was greater in those who experienced nausea. The increase fits with the progressive reduction in skin sympathetic nerve activity observed in the nauseous group. Mean blood pressure was significantly lower in those who experienced nausea and showed a much larger increase at the onset of sGVS, compared with those who did not. Moreover, the respiratory rate was higher at the outset for the subjects who experienced nausea, decreasing progressively during sGVS, whereas respiratory rate remained constant in those who did not experience nausea. Heart rate was more labile in the subjects who experienced nausea, showing a sustained increase towards the end of stimulation. We have shown that several autonomic parameters change during the nausea induced by vestibular stimulation, but a sustained decrease in skin blood flow is not a hallmark of incipient motion sickness., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

New Findings: What is the central question of this study? The impact of pulmonary arterial hypertension on open-loop baroreflex function, which determines how powerfully and rapidly the baroreflex operates to regulate arterial pressure, remains poorly understood. What is the main finding and its importance? The gain of the baroreflex total arc, indicating the baroreflex pressure-stabilizing function, is markedly attenuated in rats with monocrotaline-induced pulmonary arterial hypertension. This is caused by a rightward shift of the baroreflex neural arc and a downward shift of the peripheral arc. These findings contribute greatly to our understanding of arterial pressure regulation by the sympathetic nervous system in pulmonary arterial hypertension., Abstract: Sympathoexcitation has been documented in patients with established pulmonary arterial hypertension (PAH). Although the arterial baroreflex is the main negative feedback regulator of sympathetic nerve activity (SNA), the way in which PAH impacts baroreflex function remains poorly understood. In this study, we conducted baroreflex open-loop analysis in a rat model of PAH. Sprague-Dawley rats were injected with monocrotaline (MCT) s.c. to induce PAH (60 mg kg -1 ; n = 11) or saline as a control group (CTL; n = 8). At 3.5 weeks after MCT injection, bilateral carotid sinuses were isolated, and intrasinus pressure (CSP) was controlled while SNA at the coeliac ganglia and arterial pressure (AP) were recorded. To examine the static baroreflex function, CSP was increased stepwise while steady-state AP (total arc) and SNA (neural arc) responses to CSP and the AP response to SNA (peripheral arc) were measured. Monocrotaline significantly decreased the static gain of the baroreflex total arc at the operating AP compared with CTL (-0.80 ± 0.31 versus -0.22 ± 0.22, P < 0.05). Given that MCT markedly increased plasma noradrenaline, an index of SNA, by approximately 3.6-fold compared with CTL, calibrating SNA by plasma noradrenaline revealed that MCT shifted the neural arc to a higher SNA level and shifted the peripheral arc downwards. Monocrotaline also decreased the dynamic gain of the baroreflex total arc (-0.79 ± 0.16 versus -0.35 ± 0.17, P < 0.05), while the corner frequencies that reflect the speed of the baroreflex remained unchanged (0.06 ± 0.02 versus 0.08 ± 0.02 Hz, n.s.). In rats with MCT-induced PAH, the suppressed baroreflex peripheral arc overwhelms the augmented neural arc and, in turn, attenuates the gain of the total arc, which determines the pressure-stabilizing capacity of the baroreflex., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

New Findings: What is the central question of this study? Do sex differences exist in the cardiorespiratory responses to an isocapnic cold pressor test (CPT)? What is the main finding and its importance? During the CPT, there were no sex differences in the respiratory response; however, females demonstrated a reduced mean arterial pressure and reduced dilatation of the common carotid artery. Given that the CPT is predictive of future cardiovascular events, these data have clinical implications for improving the utility of the CPT to determine cardiovascular health risk. Sex differences should be taken into consideration when conducting and interpreting a CPT., Abstract: The cold pressor test (CPT) elicits a transient increase in sympathetic nervous activity, minute ventilation ( V ̇ E ), mean arterial pressure (MAP) and common carotid artery (CCA) diameter in healthy individuals. Although the extent of dilatation of the CCA in response to the CPT has been used as a clinical indicator of cardiovascular health status, the potential sex differences have yet to be explored. In response to a CPT, we hypothesized that elevations in V ̇ E and MAP and dilatation of the CCA would be attenuated in females compared with males. In 20 young, healthy participants (10 females), we measured the respiratory, cardiovascular and CCA responses during a CPT, which consisted of a 3 min immersion of the right foot into 0-1 ice water. Blood pressure (via finger photoplethysmography), heart rate (via electrocardiogram) and CCA diameter and velocity (via Duplex ultrasound) were simultaneously recorded immediately before and during the CPT. During the CPT, while controlling end-tidal gases to baseline values, the main findings were as follows: (i) no sex differences were present in absolute or relative changes in V ̇ E (P = 0.801 and P = 0.179, respectively); (ii) the relative MAP and CCA diameter response were reduced in females by 51 and 55%, respectively (P = 0.008 and P = 0.029 versus males, respectively); and (iii) the relative MAP responses was positively correlated with the dilatation of the CCA in males (r = 0.42, P = 0.019), in females (r = 0.43, P = 0.019) and in males and females combined (r = 0.55, P < 0.001). Given that the CPT is used as a clinical tool to assess cardiovascular health status, sex differences should be considered in future studies., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

New Findings: What is the central question of this study? Increased respiratory muscle activation is associated with neural and cardiovascular consequences via the respiratory muscle metaboreflex. Does increased sympathetic vasoconstriction originating from the respiratory musculature elicit a reduction in blood flow to an inactive limb in order to maintain blood flow to an active limb? What is the main finding and its importance? Arm blood flow was reduced whereas leg blood flow was preserved during mild leg exercise with inspiratory resistance. Blood flow to the active limb is maintained via sympathetic control of blood flow redistribution when the respiratory muscle-induced metaboreflex is activated., Abstract: The purpose of this study was to elucidate the effect of increasing inspiratory muscle work on blood flow to inactive and active limbs. Healthy young men (n = 10, 20 ± 2 years of age) performed two bilateral dynamic knee-extension and knee-flexion exercise tests at 40% peak oxygen uptake for 10 min. The trials consisted of spontaneous breathing for 5 min followed by voluntary hyperventilation either with or without inspiratory resistance for 5 min (40% of maximal inspiratory mouth pressure, inspiratory duty cycle of 50% and a breathing frequency of 40 breaths min -1 ). Mean arterial blood pressure was acquired using finger photoplethysmography. Blood flow in the brachial artery (inactive limb) and in the femoral artery (active limb) were monitored using Doppler ultrasound. Mean arterial blood pressure during exercise was higher (P < 0.05) with inspiratory resistance (121 ± 7 mmHg) than without resistance (99 ± 5 mmHg). Brachial artery blood flow increased during exercise without inspiratory resistance (120 ± 31 ml min -1 ) compared with the resting level, whereas it was attenuated with inspiratory resistance (65 ± 43 ml min -1 ). Femoral artery blood flow increased at the onset of exercise and was maintained throughout exercise without inspiratory resistance (2576 ± 640 ml min -1 ) and was unchanged when inspiratory resistance was added (2634 ± 659 ml min -1 ; P > 0.05). These results suggest that sympathetic control of blood redistribution to active limbs is facilitated, in part, by the respiratory muscle-induced metaboreflex., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

New Findings: What is the central question of this study? After sino-aortic denervation (SAD), rats present normal levels of mean arterial pressure (MAP), high MAP variability and changes in breathing. However, mechanisms involved in SAD-induced respiratory changes and their impact on the modulation of sympathetic activity remain unclear. Herein, we characterized the firing frequency of medullary respiratory neurons after SAD. What is the main finding and its importance? Sino-aortic denervation-induced prolonged inspiration was associated with a reduced interburst frequency of pre-inspiratory/inspiratory neurons and an increased long-term variability of late inspiratory neurons, but no changes were observed in the ramp-inspiratory and post-inspiratory neurons. This imbalance in the respiratory network might contribute to the modulation of sympathetic activity after SAD., Abstract: In previous studies, we documented that after sino-aortic denervation (SAD) in rats there are significant changes in the breathing pattern, but no significant changes in sympathetic activity and mean arterial pressure compared with sham-operated rats. However, the neural mechanisms involved in the respiratory changes after SAD and the extent to which they might contribute to the observed normal sympathetic activity and mean arterial pressure remain unclear. Here, we hypothesized that after SAD, rats present with changes in the firing frequency of the ventral medullary inspiratory and post-inspiratory neurons. To test this hypothesis, male Wistar rats underwent SAD or sham surgery and 3 days later were surgically prepared for an in situ experiment. The duration of inspiration significantly increased in SAD rats. During inspiration, the total firing frequency of ramp-inspiratory, pre-inspiratory/inspiratory and late-inspiratory neurons was not different between groups. During post-inspiration, the total firing frequency of post-inspiratory neurons was also not different between groups. Furthermore, the data demonstrate a reduced interburst frequency of pre-inspiratory/inspiratory neurons and an increased long-term variability of late-inspiratory neurons in SAD compared with sham-operated rats. These findings indicate that the SAD-induced prolongation of inspiration was not accompanied by alterations in the total firing frequency of the ventral medullary respiratory neurons, but it was associated with changes in the long-term variability of late-inspiratory neurons. We suggest that the timing imbalance in the respiratory network in SAD rats might contribute to the modulation of presympathetic neurons after removal of baroreceptor afferents., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

The author discusses research on the effect of chronic intermittent hypoxia (CIH) on the intrinsic electrophysiological properties of rostral ventrolateral medulla (RVLM), referencing a study by C. E. L. Almado and colleagues published in the current issue of the journal. Topics discussed include the effect of CIH on neurogenic hypertension, the challenges in measuring the activity of presympathetic neurons, and the experimental paradigm of neurogenic hypertension.

The article discusses research being done on skeletal muscle sympathetic nerve activity. It references the study "Differential Effect of Sympathetic Activation on Tissue Oxygenation in Gastroecnemius and Soleus Muscles During Exercise in Humans," by Masahiro Horiuchi and colleagues in the 2014 issue of "Experimental Physiology." The researchers examined the occurrence of sympatholysis in the gastrocnemius and soleus.

New Findings: What is the central question of this study? Water drinking increases muscle sympathetic nerve activity (MSNA), and it increases arterial blood pressure (ABP) in older populations but not in young healthy subjects. Does an increase in gain of arterial baroreflex control of MSNA contribute to maintenance of ABP after water drinking in healthy young subjects? What is the main finding and its importance? The gain of arterial baroreflex control of MSNA was increased and remained elevated 60 min after water drinking (500 ml) but remained unchanged after saline intake. An enhancement in gain of arterial baroreflex control of MSNA contributes to the maintenance of ABP after water drinking in young healthy subjects, probably via osmosensitive mechanisms., Abstract: Water drinking increases muscle sympathetic nerve activity (MSNA), which is accompanied by a profound pressor response in patients with impaired arterial baroreflex function and in older populations, but not in healthy young subjects. We tested the hypothesis that an enhancement in the gain of arterial baroreflex control of MSNA contributes to the maintenance of arterial blood pressure after water drinking in healthy young subjects. The MSNA, arterial blood pressure and heart rate were measured in 10 healthy men (24 ± 2 years old; mean ± SD) before and for 60 min after ingestion of 500 ml of bottled water or saline solution. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. After water drinking, MSNA was significantly elevated within 15 min and remained above baseline for up to 60 min [e.g. 21 ± 10 bursts (100 heart beats) -1  mmHg -1 at baseline versus 35 ± 14 bursts (100 heart beats) -1  mmHg -1 at 30 min; P < 0.01], whereas mean arterial blood pressure (e.g. 87 ± 7 mmHg at baseline versus 89 ± 7 mmHg at 30 min; P = 0.34) and heart rate were unchanged. The arterial baroreflex-MSNA gain for bursts incidence was increased and remained elevated throughout the protocol [e.g. -2.25 ± 0.99 bursts (100 heart beats) -1  mmHg -1 at baseline versus -4.32 ± 1.53 bursts (100 heart beats) -1  mmHg -1 at 30 min; P < 0.01]. Importantly, saline intake had no effect on arterial baroreflex-MSNA gain or any neurocardiovascular variables. These findings demonstrate that water drinking enhances the gain of arterial baroreflex control of MSNA in healthy young men, which may contribute to buffering the pressor response after water drinking, probably via osmosensitive mechanisms., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

New Findings: What is the central question of this research? Does acute spinal cord stimulation increase vascular conductance and decrease muscle sympathetic nerve activity in the lower limbs of humans? What is the main finding and its importance? Acute spinal cord stimulation led to a rapid rise in femoral vascular conductance, and peroneal muscle sympathetic nerve activity demonstrated a delayed reduction that was not associated with the initial increase in femoral vascular conductance. These findings suggest that neural mechanisms in addition to attenuated muscle sympathetic nerve activity might be involved in the initial increase in femoral vascular conductance during acute spinal cord stimulation., Abstract: Clinical cases have indicated an increase in peripheral blood flow after continuous epidural spinal cord stimulation (SCS) and that reduced muscle sympathetic nerve activity (MSNA) might be a potential mechanism. However, no studies in humans have directly examined the effects of acute SCS (<60 min) on vascular conductance and MSNA. In study 1, we tested the hypothesis that acute SCS (<60 min) of the thoracic spine would lead to increased common femoral vascular conductance, but not brachial vascular conductance, in 11 patients who previously underwent surgical SCS implantation for management of neuropathic pain. Throughout 60 min of SCS, common femoral artery conductance was elevated and significantly different from brachial artery conductance [in millilitres per minute: 15 min, change (Δ) 26 ± 37 versus Δ-2 ± 19%; 30 min, Δ28 ± 45 versus Δ0 ± 26%; 45 min, Δ48 ± 43 versus Δ2 ± 21%; 60 min, Δ36 ± 61 versus Δ1 ± 24%; and 15 min post-SCS, Δ51 ± 64 versus Δ6 ± 33%; P = 0.013]. A similar examination in a patient with cervical SCS revealed minimal changes in vascular conductance. In study 2, we examined whether acute SCS reduces peroneal MSNA in a subset of SCS patients (n = 5). The MSNA burst incidence in response to acute SCS gradually declined and was significantly reduced at 45 and 60 min of SCS (in bursts per 100 heart beats: 15 min, Δ-1 ± 12%; 30 min, Δ-14 ± 12%; 45 min, Δ-19 ± 16%; 60 min, Δ-24 ± 18%; and 15 min post-SCS: Δ-11 ± 7%; P = 0.015). These data demonstrate that acute SCS rapidly increases femoral vascular conductance and reduces peroneal MSNA. The gradual reduction in peroneal MSNA observed during acute SCS suggests that neural mechanisms in addition to attenuated MSNA might be involved in the acute increase in femoral vascular conductance., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

New Findings: What is the central question of this study? Premenopausal women have an attenuated inspiratory muscle metaboreflex-induced increase in arterial blood pressure compared with men. It is unclear whether sympathetic vasomotor outflow during dynamic exercise with increased inspiratory muscle activation is less in young women than in men. What is the main finding and its importance? The magnitude of increased sympathetic vasomotor outflow during leg cycling with inspiratory resistance was smaller in women than in men. Less sympathetic vasomotor outflow with inspiratory muscle metaboreflex activation could be one of the mechanisms for the attenuated inspiratory muscle-induced metaboreflex during exercise in young women., Abstract: We compared changes in muscle sympathetic nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. We hypothesized that sympathetic vasomotor outflow during exercise with increased inspiratory resistance would be attenuated in young women compared with age-matched men. Eight women and seven men completed the study. The subjects performed two 10 min exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and voluntary hyperventilation with or without inspiratory resistive breathing for 5 min (breathing frequency 50 breaths min -1 with a 50% duty cycle; inspiratory resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure (MAP) was acquired using finger photoplethysmography. The MSNA was recorded via microneurography of the right median nerve at the cubital fossa. During leg cycle exercise with inspiratory resistive breathing, MSNA burst frequency was increased, accompanied by an increase in MAP in both men and women. Women, compared with men, had less of an increase in MAP (women +22.8 ± 12.3 mmHg versus men +32.2 ± 5.4 mmHg; P < 0.05) and MSNA burst frequency (women +9.6 ± 2.9 bursts min -1 versus men +14.6 ± 6.4 bursts min -1 ; P < 0.05). These results suggest that the attenuated inspiratory muscle-induced metaboreflex during exercise in young women is attributable, in part, to a lesser sympathetic vasomotor outflow compared with men., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

New Findings: What is the topic of this review? This review briefly considers what modulates sympathetic nerve activity and how it may change as we age or in pathological conditions. It then focuses on transcutaneous vagus nerve stimulation, a method of neuromodulation in autonomic cardiovascular control. What advances does it highlight? The review considers the pathways involved in eliciting the changes in autonomic balance seen with transcutaneous vagus nerve stimulation in relationship to other neuromodulatory techniques. The autonomic nervous system, consisting of the sympathetic and parasympathetic branches, is a major contributor to the maintenance of cardiovascular variables within homeostatic limits. As we age or in certain pathological conditions, the balance between the two branches changes such that sympathetic activity is more dominant, and this change in dominance is negatively correlated with prognosis in conditions such as heart failure. We have shown that non-invasive stimulation of the tragus of the ear increases parasympathetic activity and reduces sympathetic activity and that the extent of this effect is correlated with the baseline cardiovascular parameters of different subjects. The effects could be attributable to activation of the afferent branch of the vagus and, potentially, other sensory nerves in that region. This indicates that tragus stimulation may be a viable treatment in disorders where autonomic activity to the heart is compromised., (© 2017 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the topic of this review? The C1 neurons (C1) innervate sympathetic and parasympathetic preganglionic neurons plus numerous brain nuclei implicated in stress, arousal and autonomic regulations. We consider here the contribution of C1 to stress-induced responses. What advances does it highlight? C1 activation is required for blood pressure stability during hypoxia and mild hemorrhage which exemplifies their homeostatic function. During restraint stress, C1 activate the splenic anti-inflammatory pathway resulting in tissue protection against ischemic injury. This effect, along with glucose release and, possibly, arousal are examples of adaptive non-homeostatic responses to stress that are also mediated by C1. The C1 cells are catecholaminergic and glutamatergic neurons located in the rostral ventrolateral medulla. Collectively, these neurons innervate sympathetic and parasympathetic preganglionic neurons, the hypothalamic paraventricular nucleus and countless brain structures involved in autonomic regulation, arousal and stress. Optogenetic inhibition of rostral C1 neurons has little effect on blood pressure (BP) at rest in conscious rats but produces large reductions in BP when the animals are anaesthetized or exposed to hypoxia. Optogenetic C1 stimulation increases BP and produces arousal from non-rapid eye movement sleep. C1 cell stimulation mimics the effect of restraint stress to attenuate kidney injury caused by renal ischaemia-reperfusion. These effects are mediated by the sympathetic nervous system through the spleen and eliminated by silencing the C1 neurons. These few examples illustrate that, depending on the nature of the stress, the C1 cells mediate adaptive responses of a homeostatic or allostatic nature., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

New Findings: What is the central question of this study? Sino-aortic denervated (SAD) rats present normal levels of sympathetic activity and mean arterial pressure. However, neural mechanisms regulating the sympathetic activity in the absence of arterial baroreceptors remain unclear. Considering that respiration modulates the sympathetic activity, we hypothesize that changes in the respiratory network contribute to keep the sympathetic outflow in the normal range after removal of arterial baroreceptors. What is the main finding and its importance? Despite longer inspiration observed in SAD rats, the respiratory-sympathetic coupling is working within a normal range of variation. These findings suggest that in the absence of arterial baroreceptors the respiratory modulation of sympathetic activity is maintained within the normal range. The activity of presympathetic neurons is under respiratory modulation, and changes in the central respiratory network may impact on the baseline sympathetic activity and mean arterial pressure. It is well known that after removal of baroreceptor afferents [sino-aortic denervation (SAD)], rats present an unexpected normal level of mean arterial pressure. We hypothesized that changes in the respiratory pattern and in the respiratory modulation of the sympathetic activity contribute to keep the sympathetic outflow within a normal range of variation in the absence of arterial baroreceptors in rats. To study these mechanisms, we recorded perfusion pressure and the activities of phrenic and thoracic sympathetic nerves in male juvenile rats using the working heart-brainstem preparation. The time of inspiration significantly increased in SAD rats, and this change was not dependent on the carotid bodies or on the vagal afferents. However, no changes were observed in the perfusion pressure or in the baseline thoracic sympathetic nerves in all phases of the respiratory cycle in SAD rats. Our data show that despite longer inspiratory activity, the baseline sympathetic activity is maintained at a normal level in SAD rats. These findings indicate that the respiratory-sympathetic coupling is normal after SAD and suggest that the respiratory modulation of sympathetic activity is maintained within the normal range after the removal of arterial baroreceptors., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

New Findings: What is the central question of the study? There are sex differences in the respiratory network and in the regulation of arterial blood pressure. Female rats develop hypertension after chronic intermittent hypoxia (CIH). In this context, we evaluated the respiratory-related mechanism underlying the development of hypertension in CIH-exposed female rats. What is the main finding and its importance? Female rats exposed to CIH develop changes in the respiratory pattern related to inspiration and sympathetic overactivity phase locked to the inspiratory phase of the respiratory cycle, which is different from CIH-exposed male rats. These data suggest a specific respiratory mechanism for sympathetic overactivity in hypertensive CIH-exposed female rats. Chronic intermittent hypoxia (CIH) induces sympathetic overactivity and hypertension in male rats. Enhanced respiratory modulation of sympathetic activity in juvenile male rats exposed to CIH occurs in the expiratory phase of the respiratory cycle, characterizing changes in respiratory-sympathetic coupling. Different from other experimental models of hypertension, CIH induces an increase in arterial pressure in adult female rats similar to that observed in male rats. However, the mechanisms underlying the hypertensive phenotype in CIH-exposed female rats remain to be elucidated. Moreover, several lines of evidence have documented sex differences in respiratory network activity in response to hypoxia. Considering that CIH-exposed male rats present an increase in the respiratory modulation of sympathetic activity and there are sex differences in the respiratory network, we hypothesized that CIH-exposed female rats develop an increase in the respiratory modulation of sympathetic activity different from CIH-exposed male rats. In this study, we investigated sympathetic and respiratory activities in juvenile female rats exposed to CIH using an in situ working heart-brainstem preparation. The CIH-exposed female rats developed changes in the respiratory pattern and changes in the respiratory-sympathetic coupling marked by sympathetic overactivity phase locked to inspiration, which was different from male rats exposed to CIH. This study revealed a specific respiratory-related mechanism for sympathetic overactivity linked to inspiration that explains, at least in part, the hypertensive phenotype in female rats exposed to CIH., (© 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.)

New Findings: What is the topic of this review? In this review, we discuss recent findings that provide a novel insight into the mechanisms that link glial cell function with the pathogenesis of cardiovascular disease, including systemic arterial hypertension and chronic heart failure. What advances does it highlight? We discuss how glial cells may influence central presympathetic circuits, leading to maladaptive and detrimental increases in sympathetic activity and contributing to the development and progression of cardiovascular disease. Increased activity of the sympathetic nervous system is associated with the development of cardiovascular disease and may contribute to its progression. Vasomotor and cardiac sympathetic activities are generated by the neuronal circuits located in the hypothalamus and the brainstem. These neuronal networks receive multiple inputs from the periphery and other parts of the CNS and, at a local level, may be influenced by their non-neuronal neighbours, in particular glial cells. In this review, we discuss recent experimental evidence suggesting that astrocytes and microglial cells are able to modulate the activity of sympathoexcitatory neural networks in disparate physiological and pathophysiological conditions. We focus on the chemosensory properties of astrocytes residing in the rostral ventrolateral medulla oblongata and discuss signalling mechanisms leading to glial activation during brain hypoxia and inflammation. Alterations in these mechanisms may lead to heightened activity of sympathoexcitatory CNS circuits and contribute to maladaptive and detrimental increases in sympathetic tone associated with systemic arterial hypertension and chronic heart failure., (© 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.)

New Findings: What is the topic of this review? Hypertension is a major problem in Western society. Risk of hypertension increases with age, especially in women, who have lower risk compared with men until menopause. This review outlines the sex differences in the sympathetic control of blood pressure and how these mechanisms change with age. What advances does it highlight? It has recently been recognized that men and women regulate blood pressure by different physiological mechanisms. This is important for both the understanding and the clinical management of individual patients with hypertension. This review summarizes recent advances in understanding how the regulation of blood pressure in hypertension by the sympathetic nervous system differs between men and women. The sympathetic nervous system has a central role in the regulation of arterial blood pressure (BP) and in the development of hypertension in humans. Recent evidence points to differences between the sexes in the integrative mechanisms by which BP is controlled, suggesting that the development of hypertension may follow distinct pathways in women compared with men. An important aspect of sympathetic control of BP is its substantial interindividual variability. In healthy young men, the variability in sympathetic nerve activity (SNA) is balanced by variability in cardiac output and vascular adrenergic responses, such that BP remains similar, and normal, across a severalfold range of resting SNA values. In young women, variability in resting SNA is similar to that seen in men, but the 'balancing' mechanisms are strikingly different; women exhibit greater β-adrenergic vasodilatation compared with men, which minimizes the pressor effects of a given level of SNA. Ageing is associated with increased SNA and a loss of the balancing factors seen in younger people, leading to an increased risk of hypertension in older people. Loss of oestrogen with menopause in women appears to be linked mechanistically with the decrease in β-adrenergic vasodilatation and the increased risk of hypertension in older women. Other important factors contributing to hypertension via sympathetic mechanisms are obesity and arterial stiffening, both of which increase with ageing. We conclude with a discussion of important areas in which more work is needed to understand and manage appropriately the sex-specific mechanisms in the development and maintenance of hypertension., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

New Findings: What is the topic of this review? This review considers how local dilator mechanisms and increased sympathetic nerve activity interact during acute systemic hypoxia and then reviews current understanding of some of the modifications induced by chronic hypoxia. What advances does it highlight? During acute hypoxia, local levels of hypoxia determine the release of vasodilators and magnitude of arteriolar dilatation, as well as the extent to which sympathetically evoked vasoconstriction is blunted, so maximizing distribution of O2 to muscle fibres. Chronic hypoxia in adult life and fetal programming induced by chronic hypoxia in utero lead to increased responsiveness to acute hypoxia and further blunting of sympathetic vasoconstriction, but are also associated with hypertension. In resting skeletal muscle, acute systemic hypoxia evokes vasodilatation, while vasoconstriction evoked by increased muscle sympathetic nerve activity is blunted, referred to herein as hypoxic sympatholysis. This review considers the contributions of adenosine, prostaglandin I2 , nitric oxide, ATP and endothelium-derived hyperpolarizing factors to the muscle vasodilatation, with particular attention being given to the release and actions of adenosine, which plays a dominant role. It is argued that the dilator substances are released in proportion to the local level of hypoxia, notably, allowing terminal arterioles to regulate O2 distribution through the capillaries. Correspondingly, hypoxic sympatholysis can be attributed to the ability of local hypoxia to blunt vasoconstriction evoked by noradrenaline acting on α1 - and α2 -adrenoceptors. The synergistic actions of ATP as cotransmitter may be depressed in parallel, but the actions of neuropeptide Y persist. Consideration is also given to the changes induced by chronic hypoxia in adult life and to the consequences in adult life of fetal programming induced by chronic hypoxia during pregnancy. In both conditions, dilator responsiveness to acute hypoxia is maintained, but the action or release of adenosine is altered in ways that are not yet understood. Both conditions are also accompanied by blunted sympathetically evoked vasoconstriction, tonically raised muscle sympathetic nerve activity, and increased muscular vascular tone and arterial blood pressure. With hypoxia-induced fetal programming, arterial pressure is increased in young adults and increases with age. The mechanisms underlying these changes are discussed, and it is argued that chronic hypoxia in adult life or in utero may facilitate development of hypertension., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

New Findings: What is the central question of this study? Does ageing influence the respiratory-related bursting of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure (Traube-Hering waves) that occur with respiration? What is the main finding and its importance? Despite the age-related elevation in MSNA, the cyclical inhibition of MSNA during respiration is similar between young and older individuals. Furthermore, central respiratory-sympathetic coupling plays a role in the generation of Traube-Hering waves in both young and older humans. Healthy ageing and alterations in respiratory-sympathetic coupling have been independently linked with heightened sympathetic neural vasoconstrictor activity. We investigated how age influences the respiratory-related modulation of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure that occur with respiration (Traube-Hering waves; THW). Ten young (22 ± 2 years; mean ± SD) and 10 older healthy men (58 ± 6 years) were studied while resting supine and breathing spontaneously. MSNA, blood pressure and respiration were recorded simultaneously. Resting values were ascertained and respiratory cycle-triggered averaging of MSNA and blood pressure measurements performed. The MSNA burst incidence was higher in older individuals [22.7 ± 9.2 versus 42.2 ± 13.7 bursts (100 heart beats)(-1), P < 0.05], and was reduced to a similar extent in the inspiratory to postinspiratory period in young and older subjects (by ∼ 25% compared with mid- to late expiration). A similar attenuation of MSNA burst frequency (in bursts per minute), amplitude and total activity (burst frequency × mean burst amplitude) was also observed in the inspiratory to postinspiratory period in both groups. A significant positive correlation between respiratory-related MSNA and the magnitude of Traube-Hering waves was observed in all young (100%) and most older subjects (80%). These data suggest that the strength of the cyclical inhibition of MSNA during respiration is similar between young and older individuals; thus, alterations in respiratory-sympathetic coupling appear not to contribute to the age-related elevation in MSNA. Furthermore, central respiratory-sympathetic coupling plays a role in the generation of Traube-Hering waves in both healthy young and older humans., (© 2015 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the topic of this review? This review focuses on age-related changes in the regulatory pathways that exist at the unique interface between the vascular smooth muscle and the endothelium of the skeletal muscle vasculature, and how these changes contribute to impairments in exercising skeletal muscle blood flow in the elderly. What advances does it highlight? Several recent in vivo human studies from our group and others are highlighted that have examined age-related changes in nitric oxide, endothelin-1, alpha adrenergic, and renin-angiotensin-aldosterone (RAAS) signaling. During dynamic exercise, oxygen demand from the exercising muscle is dramatically elevated, requiring a marked increase in skeletal muscle blood flow that is accomplished through a combination of systemic sympathoexcitation and local metabolic vasodilatation. With advancing age, the balance between these factors appears to be disrupted in favour of vasoconstriction, leading to an impairment in exercising skeletal muscle blood flow in the elderly. This 'hot topic' review aims to provide an update to our current knowledge of age-related changes in the neural and local mechanisms that contribute to this 'fine-tuning' of blood flow during exercise. The focus is on results from recent human studies that have adopted a reductionist approach to explore how age-related changes in both vasodilators (nitric oxide) and vasoconstrictors (endothelin-1, α-adrenergic agonists and angiotensin II) interact and how these changes impact blood flow to the exercising skeletal muscle with advancing age., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

New Findings: What is the topic of this review? The sympathetic control of renal sodium tubular reabsorption is dependent on activation of the intrarenal renin-angiotensin system and activation of the angiotensin II type 1 (AT1 ) receptor by angiotensin II. What advances does it highlight? Despite the fact that the interaction between the sympathetic nervous system and angiotensin II regarding salt reabsorption is a well-known classical mechanism for the maintenance of extracellular volume homeostasis, the underlying molecular signalling is not clearly understood. It has been shown recently that renal nerve stimulation increases intrarenal angiotensin II and activates the AT1 receptor, triggering a signalling cascade that leads to elevations of Na(+) -H(+) exchanger isoform 3-mediated tubular transport. In this short review, the crosstalk between intrarenal angiotensin II and renal nerve activity and its effect on sodium reabsorption is addressed. In this review, we address the importance of the interaction between the sympathetic nervous system and intrarenal renin-angiotensin system in modulating renal tubular handling of sodium and water. We have recently shown that increased Na(+) -H(+) exchanger isoform 3 (NHE3) activity induced by renal nerve stimulation (RNS) depends on the activation of the angiotensin II type 1 (AT1 ) receptor by angiotensin II (Ang II). Low-frequency RNS resulted in higher levels of intrarenal angiotensinogen and Ang II independent of changes in blood pressure, the glomerular filtration rate and systemic angiotensinogen. Angiotensin II, via the AT1 receptor, triggered an intracellular pathway activating NHE3 in the renal cortex, leading to antinatriuresis and antidiuresis. Pharmacological blockade of the AT1 receptor with losartan prior to RNS abolished both the functional and the molecular responses, suggesting that intrarenal Ang II acting via the AT1 receptor is a major factor for NHE3-mediated sodium and water reabsorption induced by RNS., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

New Findings: What is the topic of this review? This review focuses on the role of gap junctions and interneurones in sympathetic control at the spinal cord level. What advances does it highlight? The review considers the importance of these local spinal circuits in contributing to rhythmic autonomic activity and enabling appropriate responses to homeostatic perturbations. Sympathetic control of end organs relies on the activity of sympathetic preganglionic neurones (SPNs) within the spinal cord. These SPNs exhibit heterogeneity with respect to function, neurochemistry, location, descending inputs and patterns of activity. Part of this heterogeneity is bestowed by local spinal circuitry. Our understanding of the role of these local circuits, including the significance of connections between the SPNs themselves through specialized gap junctions, is patchy. This report focuses on interneurones and gap junctions within these circuits. Gap junctions play a role in sympathetic control; they are located on SPNs in the intermediolateral cell column. Mefloquine, a chemical that blocks these gap junctions, reduces local rhythmic activity in the spinal cord slice and disrupts autonomic control in the working heart-brainstem preparation. The role that these gap junctions may play in health and disease in adult animals remains to be elucidated fully. Presympathetic interneurones are located in laminae V, VII and X and the intermediolateral cell column; those in lamina X are GABAergic and directly inhibit SPNs. The GABAergic inputs onto SPNs exert their effects through activation of synaptic and extrasynaptic receptors, which stabilize the membrane at negative potentials. The GABAergic interneurones contribute to rhythmic patterns of activity that can be generated in the spinal cord, because bicuculline reduces network oscillatory activity. These studies indicate that local spinal cord circuitry is critical in enabling appropriate levels and patterning of activity in sympathetic outflow. We need to understand how these circuits may be harnessed in the situation of spinal cord injury., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

New Findings: What is the central question of this study? Previous studies have shown that hypersympathetic nerve activity results in ventricular electrophysiological changes and facilitates the occurrence of ventricular arrhythmias. Vagus nerve stimulation has shown therapeutic potential for myocardial infarction-induced ventricular arrhythmias. However, the actions of vagus nerve stimulation on hypersympathetic nerve activity-induced ventricular electrophysiological changes are still unknown. What is the main finding and its importance? We show that vagus nerve stimulation is able to reverse hypersympathetic nerve activity-induced ventricular electrophysiological changes and suppress the occurrence of ventricular fibrillation. These findings further suggest that vagus nerve stimulation may be an effective treatment option for ventricular arrhythmias, especially in patients with myocardial infarction or heart failure. Vagus nerve stimulation (VNS) has shown therapeutic potential for myocardial infarction-induced ventricular arrhythmias. This study aimed to investigate the effects of VNS on ventricular electrophysiological changes induced by hypersympathetic nerve activity. Seventeen open-chest dogs were subjected to left stellate ganglion stimulation (LSGS) for 4 h to simulate hypersympathetic tone. All animals were randomly assigned to the VNS group (n = 9) or the control group (n = 8). In the VNS group, VNS was performed at the voltage causing a 10% decrease in heart rate for hours 3-4 during 4 h of LSGS. During the first 2 h of LSGS, the ventricular effective refractory period (ERP) and action potential duration (APD) were both progressively and significantly decreased; the spatial dispersion of ERP, maximal slope of the restitution curve and pacing cycle length of APD alternans were all increased. With LSGS + VNS during the next 2 h, there was a significant return of all the altered electrophysiological parameters towards baseline levels. In the eight control dogs that received 4 h of LSGS without VNS, all the parameters changed progressively, but without any reversals. The ventricular fibrillation threshold was higher in the VNS group than in the control group (17.3 ± 3.4 versus 11.3 ± 3.8 V, P < 0.05). The present study demonstrated that VNS was able to reverse LSGS-induced ventricular electrophysiological changes and suppress the occurrence of ventricular fibrillation., (© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.)

The author discusses the relationship of increased blood pressure and heart rate with an increase in burst amplitude based on a study by Fazalbhoy et al. using muscle sympathetic nerve activity (MNSA) recordings. The study is part of a body of knowledge which concentrated on the importance of nerve activities and their impact on the cardiovascular system. The impact of the study by Fazalbhoy et al. on future studies of sympathetic activity, autonomic nervous system and diseases is mentioned.

Heart failure (HF) is associated with a large increase in cardiac sympathetic nerve activity (CSNA), which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is increasing evidence that arterial chemoreceptor activation plays an important role in stimulating renal sympathetic nerve activity (RSNA) and muscle sympathetic nerve activity in HF. Given that sympathetic nerve activity to individual organs is differentially controlled, we investigated whether tonic arterial chemoreceptor activation contributes to the increased CSNA in HF. We recorded CSNA and RSNA in conscious normal sheep and in sheep with mild HF induced by rapid ventricular pacing (ejection fraction <40%). Tonic arterial chemoreceptor function was evaluated by supplementing room air with 100% intranasal oxygen (2-3 l min(-1)) for 20 min, thereby deactivating chemoreceptors. The effects of hyperoxia on resting levels and baroreflex control of heart rate, CSNA and RSNA were determined. In HF, chemoreceptor deactivation induced by hyperoxia significantly reduced CSNA [90 ± 2 versus 75 ± 5 bursts (100 heart beats)(-1), P < 0.05, n = 10; room air versus hyperoxia] and heart rate (96 ± 4 versus 85 ± 4 beats min(-1), P < 0.001, n = 12). There was no change in RSNA burst incidence [93 ± 4 versus 92 ± 4 bursts (100 heart beats)(-1), n = 7], although due to the bradycardia the RSNA burst frequency was decreased (90 ± 8 versus 77 ± 7 bursts min(-1), P < 0.001). In normal sheep, chemoreceptor deactivation reduced heart rate without a significant effect on CSNA or RSNA. In summary, deactivation of peripheral chemoreceptors during HF reduced the elevated levels of CSNA, indicating that tonic arterial chemoreceptor activation plays a critical role in stimulating the elevated CSNA in HF., (© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.)