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Along with well-known data on the neurochemical mechanisms of nociceptor activation, there are still no clear data regarding changes in the cellular composition and morphological characteristics of spinal preganglionic neurons (SPN) after capsaicin treatment. The mechanism of capsaicin toxicity differs in developing and mature nerve cells. This study aimed to determine the number of SPN in the autonomic nuclei on spinal cord (SC) sections and their cross-sectional area, the localization, percentage, and profile area of SPN containing neuronal nitric oxide synthase (nNOS) and calbindin (CB) in the thoracic SC of rats of different ages (from birth to 1-year-old) after capsaicin treatment. Neonatal capsaicin treatment generally decreased the cross-sectional area of the SPN pericarya. However, the cross-sectional area of the CB-immunoreactive (IR) SPN increased in the central autonomic area in rats aged 10-30 days old after capsaicin treatment. The number of SPN decreased only in the central autonomic area of rats aged <20 days. The proportion of nNOS-IR neurons remained steady and did not change during development. The cross-sectional area of nNOS-IR SPN in capsaicin-treated rats was less than that in control rats. The results obtained will promote further studies on the mechanisms of sensory processing in the SC and the development of the sympathetic nervous system., (© 2022 American Association for Anatomy.)

The sympathetic nervous system inhibits gut motility, secretion, and blood flow in the gut microvasculature and can modulate gastrointestinal inflammation. Sympathetic neurons signal via catecholamines, neuropeptides, and gas mediators. In the current review, we summarize the current understanding of the mature sympathetic innervation of the gastrointestinal tract with a focus mainly on the prevertebral sympathetic ganglia as the main output to the gut. We also highlight recent work regarding the developmental processes of sympathetic innervation. The anatomy, neurochemistry, and connections of the sympathetic prevertebral ganglia with different parts of the gut are considered in adult organisms during prenatal and postnatal development and aging. The processes and mechanisms that control the development of sympathetic neurons, including their migratory pathways, neuronal differentiation, and aging, are reviewed., (© 2022 American Association for Anatomy.)

The pressor response induced by a voluntary hypoxic apnea is mediated largely by increased sympathetic outflow. The neural control of blood pressure is altered in recovery from acute heat exposure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. Therefore, we tested the hypothesis that prior heat exposure would attenuate the pressor response induced by a voluntary hypoxic apnea. Eleven healthy adults (five women) were exposed to whole body passive heating (water-perfused suit) sufficient to increase body core temperature by 1.2°C. Voluntary hypoxic apneas were performed at baseline and in recovery when body core temperature returned to ≤ 0.3°C of baseline. Participants breathed gas mixtures of varying [Formula: see text] (21%, 16%, and 12%; randomized) for 1 min followed by a 15-s end-expiratory apnea. The change in arterial oxygen saturation during each apnea did not differ from baseline to recovery ( P = 0.6 for interaction), whereas the pressor response induced by a voluntary hypoxia apnea was reduced ([Formula: see text] 21%, baseline 17 ± 7 mmHg vs. recovery 14 ± 7 mmHg; [Formula: see text] 16%, baseline 24 ± 8 mmHg vs. recovery 18 ± 7 mmHg; [Formula: see text] 12%, baseline 28 ± 11 mmHg vs. recovery 24 ± 11 mmHg; P = 0.01 for main effect of time). These data suggest that prior heat exposure induces a cross-stressor effect such that the pressor response to a voluntary hypoxic apnea is attenuated. NEW & NOTEWORTHY The pressor response induced by a voluntary hypoxic apnea is mediated by increased sympathetic outflow. The neural control of blood pressure is altered in recovery from acute heat exposure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. Our data suggest that prior heat exposure induces a cross-stressor effect such that the pressor response to a voluntary hypoxic apnea is attenuated.

Purpose: We sought to investigate the sympathetic mechanism controlling coronary circulation during trigeminal nerve stimulation in healthy women., Methods: The protocol consisted of 3 min of trigeminal nerve stimulation (TGS) with cold stimuli to the face, in two conditions: (1) control and β-blockade (oral propranolol), and (2) control and α-blockade (oral prazosin)., Results: Thirty-one healthy young subjects (women: n = 13; men: n = 18) participated in the study. By design, TGS decreased heart rate (HR), and increased blood pressure (BP) and cardiac output (CO). Before the β-blockade coronary blood velocity (CBV-Δ1.4 ± 1.3 cm s -1 ) increased along with the decrease of coronary vascular conductance index (CVCi-Δ-0.04 ± 0.04 cm s -1  mmHg -1 ) during TGS and the β-blockade abolished the CBV increase and a further decrease of CVCi was observed with TGS (Δ-0.06 ± 0.07 cm s -1  mmHg -1 ). During the α-blockade condition before the blockade, the CBV increased (Δ0.93 ± 1.48 cm s -1 ) along with the decrease of CVCi (Δ-0.05 ± 1.12 cm s -1  mmHg -1 ) during TGS, after the α-blockade CBV (Δ0.98 ± cm s -1 ) and CVCi (Δ-0.03 ± 0.06 cm s -1  mmHg -1 ) response to TGS did not change., Conclusion: Coronary circulation increases during sympathetic stimulation even with a decrease in heart rate., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Few studies have investigated skin blood flow in children and age-related differences in the underlying mechanisms. We examined mechanisms of skin blood flow responses to local heating, postocclusive reactive hyperaemia (PORH), and isometric handgrip exercise in adult and prepubescent males, hypothesizing that skin blood flow responses would be greater in children compared with adults. We measured skin blood flow in 12 boys (age, 9 ± 1 years) and 12 men (age, 21 ± 1 years) using laser-Doppler flowmetry at rest, in response to 3-min PORH, 2-min isometric handgrip exercise, and local skin heating to 39 °C (submaximal) and 44 °C (maximal). Using wavelet analysis we assessed endothelial, neural, and myogenic activities. At rest and in response to local heating to 39 °C, children had higher skin blood flow and endothelial activity compared with men (d ≥ 1.1, p < 0.001) and similar neurogenic and myogenic activities (d < 0.2, p > 0.05). Maximal responses to 44 °C local skin heating, PORH, and isometric handgrip exercise did not differ between boys and men (all d ≤ 0.2, p > 0.05). During PORH children demonstrated greater endothelial activity compared with men (d ≥ 0.6, p < 0.05); in contrast, men had higher neurogenic activity (d = 1.0, p < 0.01). During isometric handgrip exercise there were no differences in endothelial, neurogenic, and myogenic activities (d < 0.2, p > 0.3), with boys and men demonstrating similar increases in endothelial activity and decreases in myogenic activity (d ≥ 0.8, p < 0.05). These data suggest that boys experience greater levels of skin blood flow at rest and in response to submaximal local heating compared with men, while maximal responses appear to be similar. Additionally, endothelial mediators seem to contribute more to vasodilatation in boys than in men. [ABSTRACT FROM AUTHOR]

Sympathetic nervous system (SNS) is a part of the autonomic nervous system which involuntarily regulates internal body functions. It appears to modulate the processing of nociceptive information. Many orofacial pain conditions involve inflammation of orofacial tissues and/or injury of nerve, some of which might be attributed to SNS. Thus, the aim of this review was to bring together the data available regarding the peripheral sympathetic mechanisms involved in orofacial pain. A clearer understanding of SNS–sensory interactions in orofacial pain may provide a basis for novel therapeutic strategies for conditions that respond poorly to conventional treatments. [ABSTRACT FROM AUTHOR]

Highlights • β-Eudesmol decreases efferent adrenal sympathetic nerve activity (ASNA). • Stomach may be critical organ for the β-eudesmol effect on ASNA. • TRPA1 channel is involved in β-eudesmol effect on ASNA. Abstract The autonomic nervous system innervates various peripheral tissue functions. Various external stimuli affect autonomic nerve activity, however, there is little information about the involvement of sensory receptors in the responses. The TRPA1 is a calcium-permeable non-selective cation channel which plays a crucial role in the susceptibility to various stimuli. β-Eudesmol, an oxygenated sesquiterpene found in hop essential oil and beer, activates the TRPA1. Intragastric administration of β-eudesmol decreased efferent adrenal sympathetic nerve activity (ASNA) in rats, whereas subcutaneous administration did not. ASNA suppression by β-eudesmol was not observed in TRPA1 knockout rats. The β-eudesmol derived ASNA suppression was partially, but significantly, eliminated by subdiaphragmatic vagotomy in rats, suggesting the afferent vagal nerve from the gastrointestinal tract to the brain is involved in the effect of β-eudesmol on ASNA. Our results indicate that β-eudesmol suppresses ASNA, partly through TRPA1 and the afferent vagus nerve. These findings introduce the physiological significance of the TRPA1 in the control of ASNA. [ABSTRACT FROM AUTHOR]

Cardiac autonomic balance (CAB), defined as the relative influences of the sympathetic (SNS) and parasympathetic (PNS) nervous systems on the heart at rest, is a well-established biomarker of mental and physical health in adulthood (Kemp & Quintana, 2013). SNS and PNS functioning that, jointly, determine CAB, mature and stabilize between gestation and age five (Alkon, Boyce, Davis, & Eskenazi, 2011), co-developing with capacity to regulate distress during challenge and social engagement (Porges & Furman, 2011). This review integrates existing work in developmental, clinical, and medical sciences to propose a theoretical model of CAB development from gestation through early childhood and its putative relations with later functioning. By age five, CAB may reflect biological embedding of regulatory strategies that lay the groundwork for risk or resilience: The same profiles of SNS and PNS functioning associated with limited regulatory support in infancy and exposure to early adversity predict poor mental and physical health problems in adulthood (e.g., Beauchaine, 2001; Oosterman et al., 2010; Suurland, van der Heijden, Smaling, et al., 2017). In three key questions, we identify areas of consensus and remaining gaps in existing work to guide the next generation of research on early CAB development as a possible pathway from early experiences to mental and physical health outcomes. [ABSTRACT FROM AUTHOR]

Augmented sympathetic nerve activity is associated with heart failure with preserved left ventricular ejection fraction (HFpEF). Lipophilic statins reduce sympathetic nerve activity in patients with heart failure with reduced left ventricular ejection fraction. However, little is known about whether all types of statins, regardless of solubility, reduce sympathetic nerve activity in HFpEF. We evaluated the effect of atorvastatin, a lipophilic statin, and rosuvastatin, a hydrophilic statin, on muscle sympathetic nerve activity (MSNA) in HFpEF patients. This study was conducted as a prospective, randomized, open-label, crossover trial. Ten HFpEF patients with untreated hyperlipidemia participated in this study. Subjects were assigned to either the atorvastatin (lipophilic) or the rosuvastatin (hydrophilic) group with each drug administered for 8 weeks. Atorvastatin and rosuvastatin treatment resulted in a similar reduction in low-density lipoprotein cholesterol (LDL-C) levels. There was no difference in the effect of either treatment on blood pressure, heart rate, or left ventricular function. Atorvastatin significantly decreased MSNA frequency compared with baseline (31.5 ± 6.3 vs. 47.5 ± 10.7 bursts/min, p < 0.01), but rosuvastatin had no effect on MSNA (40.9 ± 7.3 bursts/min). MSNA was significantly lower in the atorvastatin group than rosuvastatin group (p < 0.05). However, the reduction in MSNA seen in either group did not correlate with the reduction in LDL-C. No significant differences were observed in either the baroreflex control of heart rate or MSNA between the two groups. These results suggest that lipophilic statins have a favorable effect on sympathetic nerve activity beyond lowering LDL-C in HFpEF, but hydrophilic statins do not. [ABSTRACT FROM AUTHOR]

The present study investigates how coordination between stress responsivity of the parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) moderates the prospective effects of marital conflict on internalizing and externalizing symptoms across adolescence. Although an important avenue for psychophysiological research concerns how PNS and SNS responses jointly influence adjustment in the context of stress, these processes have rarely been studied in adolescence or longitudinally. Participants were 252 youth (53% female, 66% European American, 34% African American) who participated in laboratory assessments when they were 16, 17, and 18 years old. PNS activity (measured via respiratory sinus arrhythmia [RSA]) and SNS activity (measured via skin conductance level [SCL]) were assessed during a resting baseline and in response to a laboratory-based challenge (star tracing). Parents and adolescents both reported on marital conflict and adolescents reported on their internalizing and externalizing symptoms. At higher levels of marital conflict, coactivation of PNS and SNS activity, characterized by increased RSA and increased SCL from baseline to challenge, predicted elevated internalizing symptoms and an increase in externalizing behavior across adolescence. Coinhibition, or decreased activity across both systems, also predicted an increase in internalizing symptoms over time. At lower levels of marital conflict, internalizing and externalizing symptoms were relatively low. Findings extend primarily cross-sectional work with younger children by demonstrating that coordination between the two branches of the autonomic nervous system (ANS) moderates the longitudinal effects of marital conflict on psychological and behavioral maladjustment among adolescents. [ABSTRACT FROM AUTHOR]

Multiple theoretical frameworks posit that interactions between the autonomic nervous system and higher-order neural networks are crucial for cognitive regulation. However, few studies have simultaneously examined autonomic physiology and brain activity during cognitive tasks. Such research is promising for understanding how early adversity impacts neurocognitive development in children, given that stress experienced early in life impacts both autonomic function and regulatory behaviors. We recorded event-related potentials (ERPs) as a neural measure of auditory selective attention, and cardiovascular measures of high-frequency heart rate variability (HF-HRV) and preejection period (PEP), in 105 3-5-year-old children with varying degrees of socioeconomic risk. First, we replicated a previous study from our lab: Increased socioeconomic risk was associated with larger ERP amplitudes elicited by distracting sounds. Next, we tested whether PEP and HF-HRV (at rest and during the task) were associated with the distractor ERP response, and found that a physiological profile marked by heightened sympathetic nervous system activity, indexed by shorter PEP, was associated with better ERP suppression of distractor sounds in lower SES children. Finally, we found that PEP mediated the relationship between socioeconomic risk and larger ERP responses to distractor sounds. In line with similar reports, these results suggest that for lower SES children, there is a potential biological cost of achieving better cognitive performance, seen here as increased cardiovascular arousal both at rest and in response to task demands. [ABSTRACT FROM AUTHOR]

A burgeoning literature supports the role of autonomic nervous system (ANS) functioning as an index of physiologic sensitivity to the environment, but extant research is limited in its focus on single branches of the ANS, childhood samples, and solely negative environmental factors. This study seeks to address these limitations by exploring whether reactivity in the parasympathetic (PNS) and sympathetic (SNS) nervous systems jointly moderate the prospective contributions of both positive (maternal involvement) and negative (maternal psychological control) aspects of the family environment to developmentally relevant outcomes in adolescence (depressive symptoms and emotion regulation). At Wave 1, adolescents (n = 352, 52% female, M age = 15.27, SD = 1.04; 65% White) and their parents completed a problem-solving discussion task, during which adolescent ANS activation was continuously monitored, and reports of maternal involvement, maternal psychological control, adolescent depressive symptoms, and adolescent emotion regulation were obtained. Adolescent depressive symptoms and emotion regulation were assessed again 1 year later (Wave 2). Results indicated that PNS and SNS reactivity jointly moderated the prospective contributions of maternal involvement and maternal psychological control to depressive symptoms and emotion regulation. Specifically, adolescents who exhibited reciprocal SNS activation appeared to be most sensitive to both positive and negative parenting environments. Adolescents exhibiting coinhibition or coactivation profiles of autonomic reactivity were comparatively unreactive to parenting. This study corroborates the notion that consideration of multiple physiological systems is critical to our understanding of biological processes in the development of emotional functioning in adolescence. [ABSTRACT FROM AUTHOR]

Highlights • Effects of tonic sympathetic (SNS) activation on negative urgency were examined. • Higher SNS activity strengthened the association between neuroticism and urgency. • SNS also strengthened the link between neuroticism and hostile reactivity to stress. • Lower SNS strengthened link between neuroticism and shame reactivity to stress. • Hostile reactivity partially mediated the moderating effect of SNS on urgency. Abstract The tendency to engage in impulsive behavior in the context of negative affect, known as negative urgency, has emerged as a powerful transdiagnostic predictor of behavioral dysregulation. Although general vulnerability to negative affect (neuroticism) correlates with negative urgency, not all neurotic individuals engage in urgent behavior. Given prior experimental evidence that sympathetic nervous system (SNS) activation may promote emotion-related impulsivity, the present study examines tonic SNS activity as a moderator of the link between neuroticism and negative urgency. Participants (N = 194) completed measures of neuroticism and negative urgency, as well as a stress task. They also underwent assessment of tonic SNS activity (cardiac pre-ejection period). The link between neuroticism and negative urgency was strengthened for individuals with higher tonic SNS activity; however, this was not the case for behavioral performance on the task. A similar pattern was demonstrated for hostile reactivity to the stress task; increased hostile response partially explained the interaction between SNS activation and neuroticism on negative urgency. These findings suggest a potential facilitative role of the SNS in hostile reactivity and emotion-driven impulsivity among more neurotic individuals. [ABSTRACT FROM AUTHOR]

The medullary raphé nuclei are involved in controlling cardiovascular, respiratory, and thermoregulatory functions, as well as mediating stress-induced tachycardia and hyperthermia. Although the serotonergic system of the medullary raphé has been suggested as the responsible entity, specific evidence has been insufficient. In the present study, we tested this possibility by utilizing an optogenetic approach. We used genetically modified mice [tryptophan hydroxylase 2 (Tph2); archaerhodopsin-T (ArchT) mice] in which ArchT, a green light-driven neuronal silencer, was selectively expressed in serotonergic neurons under the regulation of Tph2 promoters. We first confirmed that an intruder stress selectively activated medullary, but not dorsal or median raphé serotonergic neurons. This activation was suppressed by photo-illumination via a pre-implanted optical fiber, as evidenced by the decrease of a cellular activation marker protein in the neurons. Next, we measured electro cardiogram (ECG), respiration, body temperature (BT), and locomotor activity in freely moving mice during intruder and cage-drop stress tests, with and without photo-illumination. In the intruder test, photo inactivation of the medullary serotonergic neurons significantly attenuated tachycardia (362 ± 58 vs. 564 ± 65 bpm.min, n = 19, p = 0.002) and tachypnea (94 ± 82 vs. 361 ± 138 cpm.min, n = 9, p = 0.026), but not hyperthermia (1.0 ± 0.1 vs. 1.0 ± 0.1°C.min, n = 19, p = 0.926) or hyperlocomotion (17 ± 4 vs. 22 ± 4, arbitrary, n = 19, p = 0.089). Similar results were obtained from cage-drop stress testing. Finally, photo-illumination did not affect the basal parameters of the resting condition. We conclude that a subpopulation of serotonergic neurons in the medullary raphé specifically mediate stress-induced tachypnea and tachycardia, which have little involvement in the basal determination of respiratory frequency (Res) and heart rate (HR), specifically mediate stress-induced tachycardia and tachypnea. [ABSTRACT FROM AUTHOR]

Short- to medium-term (i.e., 4-14 days) heating protocols induce physiological adaptations including improved cardiac autonomic modulations, as assessed using heart rate variability, which may contribute to greater exercise performance. Whether similar cardiac autonomic changes occur during an intense heating protocol (sauna) reported to increase plasma volume in athletes remains to be confirmed. This study examined changes in heart rate and its variability during a single extreme heat (sauna) exposure and repeated exposures in athletes. Six well-trained male cyclists undertook sauna bathing (30 min, 87 °C, 11% relative humidity) immediately after normal training over 10 consecutive days. Heart rate recordings were obtained during each sauna bout. Heart rate and its variability (natural logarithm of root mean square of successive differences, lnRMSSD) were analysed during 10-min periods within the first bout, and changes in heart rate and lnRMSSD were analysed during each bout via magnitude-based inferences. During the first sauna bout, heart rate was almost certainly increased (∼32%, effect size 1.68) and lnRMSSD was almost certainly reduced (∼62%, effect size -5.21) from the first to the last 10-min period, indicating reduced parasympathetic and (or) enhanced sympathetic modulations. Acute exposure to extreme heat stress via sauna produced alterations in heart rate and cardiac autonomic modulations with successive postexercise heat exposures producing unclear changes over a 10-day period. The physiological benefits of intense heating via sauna on cardiac control in athletes remain to be elucidated. [ABSTRACT FROM AUTHOR]

Background: The recycling of citrulline by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL) is crucial to maintain arginine availability and nitric oxide (NO) production. Pegylated arginine deiminase (ADI-PEG20) is a bacterial enzyme used to deplete circulating arginine.Objective: The goal of this research was to test the hypothesis that citrulline is able to sustain intracellular arginine availability for NO production in ADI-PEG20 arginine-depleted mice.Methods: Six- to 8-wk-old male C57BL/6J mice injected with ADI-PEG20 (5 IU) or saline (control) were used in 4 different studies. Arginine, citrulline, and NO kinetics were determined by using stable isotopes in unchallenged (study 1) and endotoxin-challenged (study 2) mice. Blood pressure was determined by telemetry for 6 d after ADI-PEG20 administration (study 3), and vasomotor activity and ASS1 and ASL gene expression were determined in mesenteric arteries collected from additional mice (study 4).Results: ADI-PEG20 administration resulted in arginine depletion (<1 compared with 111 ± 37 µmol/L) but in greater plasma citrulline concentrations (900 ± 123 compared with 76 ± 8 µmol/L; P < 0.001) and fluxes (402 ± 17 compared with 126 ± 4 µmol ⋅ kg-1 ⋅ h-1; P < 0.001) compared with controls. Endotoxin-challenged ADI-PEG20-treated mice produced less NO than controls (13 ± 1 compared with 27 ± 2 µmol ⋅ kg-1 ⋅ h-1; P < 0.001). No differences (P > 0.50) were observed for cardiovascular variables (heart rate, blood pressure) between ADI-PEG20-treated and control mice. Furthermore, no ex vivo vasomotor differences were observed between the 2 treatments. ADI-PEG20 administration resulted in greater gene expression of ASS1 (∼3-fold) but lower expression of ASL (-30%).Conclusion: ADI-PEG20 successfully depleted circulating arginine without any effect on cardiovascular endpoints in healthy mice but limited NO production after endotoxin challenge. Therefore, the citrulline recycling pathway can sustain local arginine availability independently from circulating arginine, satisfying the demand of arginine for endothelial NO production; however, it is unable to do so when a high demand for arginine is elicited by endotoxin. [ABSTRACT FROM AUTHOR]

Background: Uncoupling protein 1 (UCP1) plays an important role in increasing energy expenditure; thus, it is being considered as a new target for preventing obesity and metabolic complications. In this study, we investigated the effect of quercetin, a naturally occurring flavonoid, on UCP1 expression in white/brown adipose tissues (WAT/BAT). Methods: Mice were fed a high-fat diet (HFD) supplemented with or without dietary quercetin for 9 weeks, and 3T3-L1 adipocytes were treated with quercetin. Expression of UCP1 and other thermogenic genes/proteins was measured by real-time polymerase chain reaction and/or Western blotting. Results: Dietary quercetin supplementation increased the level of UCP1 in both WAT and/or BAT of HFD-fed obese mice, which was accompanied by upregulated mRNA levels of thermogenesis-related genes. Quercetin supplementation enhanced the plasma norepinephrine level and tended to upregulate ß-adrenergic receptor mRNA level in the WAT of HFD-fed obese mice, accompanied by AMP-activated protein kinase (AMPK) activation. Moreover, quercetin enhanced UCP1 expression in 3T3-L1 adipocytes, and this was blunted by treatment with a peroxisome proliferator-activated receptor gamma (PPARγ) antagonist. Conclusion: These findings suggest that quercetin upregulates UCP1, implying increased WAT browning and BAT activity, via activation of the AMPK/PPARγ pathway through sympathetic stimulation. Quercetin may be useful for preventing obesity and metabolic complications. [ABSTRACT FROM AUTHOR]

Purpose: Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Methods: Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. Results: After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P < 0.001), maximal heart rate (-2 ± 4 vs -8 ± 3 bpm, P = 0.006), heart rate variability (SD of normal-to-normal intervals, 27 ± 31 vs -3 ± 25 ms; P = 0.04), and cardiac BRS (7±6 vs -2 ± 8 ms-mm Hg-1, P = 0.02) differed between the control and overload groups. The change in MSNA burst frequency (-2 ± 2vs4 ± 5 bursts per minute, P = 0.02) differed between groups. Across all participants, the changes in resting MSNA and peak power output were correlated negatively (r = -0.51, P = 0.04). No between-group differences in resting heart rate or blood pressure were observed (all P > 0.05). Conclusions: Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance. [ABSTRACT FROM AUTHOR]

Purpose: This preliminary study tested the hypothesis that the carotid baroreflex (CBR) mediated sympathoexcitation regulates cerebral blood flow (CBF) at rest and during dynamic exercise.Methods: In seven healthy subjects (26 ± 1 years), oscillatory neck pressure (NP) stimuli of + 40 mmHg were applied to the carotid baroreceptors at a pre-determined frequency of 0.1 Hz at rest, low (10 ± 1W), and heavy (30 ± 3W) exercise workloads (WLs) without (control) and with α - 1 adrenoreceptor blockade (prazosin). Spectral power analysis of the mean arterial blood pressure (MAP), mean middle cerebral artery blood velocity (MCAV), and cerebral tissue oxygenation index (ScO2) in the low-frequency range (0.07-0.20 Hz) was estimated to examine NP stimuli responses.Results: From rest to heavy exercise, WLs resulted in a greater than three-fold increase in MCAV power (42 ± 23.8-145.2 ± 78, p < 0.01) and an almost three-fold increase in ScO2 power (0.51 ± 0.3-1.53 ± 0.8, p = 0.01), even though there were no changes in MAP power (from 24.5 ± 21 to 22.9 ± 11.9) with NP stimuli. With prazosin, the overall MAP (p = 0.0017), MCAV (p = 0.019), and ScO2 (p = 0.049) power was blunted regardless of the exercise conditions. Prazosin blockade resulted in increases in the Tf gain index between MAP and MCAV compared to the control (p = 0.03).Conclusion: CBR-mediated changes in sympathetic activity contribute to dynamic regulation of the cerebral vasculature and CBF at rest and during dynamic exercise in humans. [ABSTRACT FROM AUTHOR]

The choroid is richly innervated by parasympathetic, sympathetic and trigeminal sensory nerve fibers that regulate choroidal blood flow in birds and mammals, and presumably other vertebrate classes as well. The parasympathetic innervation has been shown to vasodilate and increase choroidal blood flow, the sympathetic input has been shown to vasoconstrict and decrease choroidal blood flow, and the sensory input has been shown to both convey pain and thermal information centrally and act locally to vasodilate and increase choroidal blood flow. As the choroid lies behind the retina and cannot respond readily to retinal metabolic signals, its innervation is important for adjustments in flow required by either retinal activity, by fluctuations in the systemic blood pressure driving choroidal perfusion, and possibly by retinal temperature. The former two appear to be mediated by the sympathetic and parasympathetic nervous systems, via central circuits responsive to retinal activity and systemic blood pressure, but adjustments for ocular perfusion pressure also appear to be influenced by local autoregulatory myogenic mechanisms. Adaptive choroidal responses to temperature may be mediated by trigeminal sensory fibers. Impairments in the neural control of choroidal blood flow occur with aging, and various ocular or systemic diseases such as glaucoma, age-related macular degeneration (AMD), hypertension, and diabetes, and may contribute to retinal pathology and dysfunction in these conditions, or in the case of AMD be a precondition. The present manuscript reviews findings in birds and mammals that contribute to the above-summarized understanding of the roles of the autonomic and sensory innervation of the choroid in controlling choroidal blood flow, and in the importance of such regulation for maintaining retinal health. [ABSTRACT FROM AUTHOR]

Background: The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization instability in humans. Methods and Results: Heart failure patients with cardiac resynchronization therapy defibrillator devices (n = 11) had activation recovery intervals (ARI, surrogate for APD) recorded from left ventricular epicardial electrodes alongside simultaneous non-invasive blood pressure and respiratory recordings. Fixed cycle length was achieved by right ventricular pacing. Recordings took place during resting conditions and following an autonomic stimulus (Valsalva). The variability of ARI and the normalized variability of ARI showed significant increases post Valsalva when compared to control (p = 0.019 and p = 0.032, respectively). The oscillatory behavior was quantified by spectral analysis. Significant increases in low frequency (LF) power (p = 0.002) and normalized LF power (p = 0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behavior of conduction. However, increases in the LF power of ARI were accompanied by increases in the LF power of systolic blood pressure (SBP) and the rate of systolic pressure increase (dP/dtmax). Positive correlations were found between LF-SBP and LF-dP/dtmax (rs = 0.933, p < 0.001), LF-ARI and LF-SBP (rs = 0.681, p = 0.001) and between LF-ARI and LF-dP/dtmax (rs = 0.623, p = 0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs = 0.679, p < 0.001). Conclusions: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (~0.1Hz) of left ventricular APD with a strong positive correlation between the LF power of APD and the BBV of APD. These findings may be of importance in mechanisms underlying stability/instability of repolarization and arrhythmogenesis in humans. [ABSTRACT FROM AUTHOR]

Unequivocal enhancement of cutaneous vasomotor function has yet to be demonstrated following heat acclimation, possibly because the adaptation stimulus was not sustained, or because thermoeffector function was not assessed at equivalent deep-body temperatures. Therefore, forearm and local cutaneous vascular conductances were evaluated during exercise eliciting matched deep-body temperatures (37.5 °C, 38.5 °C), before and after isothermal heat acclimation. Both indices increased (21% and 25%), confirming cutaneous vasomotor adaptation can occur, provided those experimental design specifications are satisfied. [ABSTRACT FROM AUTHOR]

Purpose: Increased resting muscle sympathetic nerve activity (MSNA) and lower forearm blood flow (FBF) were observed in young men who use anabolic androgenic steroids (AAS). However, the response of MSNA and FBF in AAS users triggered by muscle mechanoreflex and central command has never been tested. In addition, we evaluated the blood pressure (BP) and heart rate (HR) responses during these maneuvers. Methods: Nineteen AAS users (AASU) 31 ± 6 yr of age and 18 AAS nonusers (AASNU) 29 ± 4 yr of age were recruited. All participants were involved in strength training. AAS use was determined using a urine test (liquid chromatography with tandem mass spectrometry). MSNA was measured using the microneurography technique. FBF was measured by using venous occlusion plethysmography. BP was measured using an automatic oscillometric device. HR was recorded continuously through ECG. Isometric handgrip exercise was performed at 30% of the maximal voluntary contraction for 3 min, and mental stress was elicited by the Stroop color-word test for 4 min. Results: The MSNA and FBF responses during exercise were similar between AASU and AASNU, with a trend toward higher MSNA (bursts per minute; P = 0.084) and lower forearm vascular conductance (FVC; units; P = 0.084) in AASU than in AASNU. During mental stress, AASU showed a significantly higher MSNA (P G 0.05) and lower FBF (P < 0.05) compared with AASNU. During both maneuvers, HR and BP increased linearly in both groups; however, AASU showed a significantly higher HR compared with AASNU. Conclusions: During muscle mechanoreflex activation (isometric exercise), AASU have normal MSNA and FBF responses, whereas during central command (mental stress) stimulation, AASU have exacerbated MSNA and blunted vasodilation. Therefore, mental stress seems to exacerbate neurovascular control throughout stress reaction situations in AASU. [ABSTRACT FROM AUTHOR]

Combined results from different independent studies suggest that acclimatization to high altitude induces a slowly developing sympathetic activation, even at levels of hypoxia that cause no acute chemoreflex‐mediated sympathoexcitation. We here provide direct neurophysiological evidence for this phenomenon. In eight Danish lowlanders, we quantified mean arterial blood pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA), twice at sea level (normoxia and with acute hypoxic exposure to 12.6% O2) and twice at high altitude (after 10 and 50 days of exposure to 4100 m). Measurements were also obtained in eight Bolivian highlanders on one occasion at high altitude. Acute hypoxic exposure caused no increase in MSNA (15 ± 2 vs 16 ± 2 bursts per min, respectively, and also MAP and HR remained stable). In contrast, from sea level to 10 and 50 days in high‐altitude increases were observed in MAP: 72 ± 2 vs 78 ± 2 and 75 ± 2 mm Hg; HR: 54 ± 3 vs 67 ± 3 and 65 ± 3 beats per min; MSNA: 15 ± 2 vs 42 ± 5 and 42 ± 5 bursts per min, all P < .05. Bolivian subjects had high levels of MSNA: 34 ± 4 bursts per min. The simultaneous increase in MAP, HR, and MSNA suggests high altitude‐induced sympathetic activity, which is sustained in well‐acclimatized lowlanders. The high MSNA levels in the Bolivian highlanders suggest lifelong sympathetic activation at high altitude. [ABSTRACT FROM AUTHOR]

In pathological populations, elevated sympathetic activity is associated with increased activity of individual sympathetic neurons. We used custom action potential detection software to analyze multiunit sympathetic activity in 18 normotensive pregnant women (third trimester; 33 ± 5 wk) and 19 nonpregnant women at rest and a subset (10 and 13, respectively) during a cold pressor challenge. Although the number of action potentials per burst and number of active amplitude-based "clusters" were not different between groups, the total number of sympathetic action potentials per minute was higher in pregnant women at rest. Individual clusters were active predominately once per burst, suggesting they represent single neurons. Action potentials occurred in closer succession in normotensive pregnant (interspike interval 36 ± 10 ms) versus nonpregnant women (50 ± 27 ms; P 0.001) at rest. Pregnant women had a lower total peripheral resistance (11.7 ± 3.0 mmHg·l-1·min) than nonpregnant women (15.1 ± 2.7 mmHg·l-1·min; P < 0.001), indicating a blunted neurovascular transduction. The cold pressor reduced the number of action potentials per burst in both groups due to shortening of the R-R interval in conjunction with increased burst frequency; total neural firing per minute was unchanged. Thus elevated sympathetic activity during normotensive pregnancy is specific to increased incidence of multiunit bursts. This is likely due to decreased central gating of burst output as opposed to generalized increases in central drive. These data also reinforce the concept that pregnancy appears to be the only healthy state of chronic sympathetic hyperactivity of which we are aware. [ABSTRACT FROM AUTHOR]

Self-injurious thoughts and behaviors are used to escape or regulate aversive physiological states during stress. Low sympathetic nervous system arousal during stress has been shown to confer risk. This risk may be exacerbated by trait impulsivity; adolescents high in impulsivity are more likely to rashly use maladaptive regulation strategies. We examined this relationship longitudinally in a sample of adolescents ages 10 to 14 (55.4% female) from the United States. Consistent with our hypothesis, low arousal during stress and high trait impulsivity interacted to predict the use of self-injurious thoughts and behaviors over a six-month period. This study extends and clarifies previous research findings regarding the relationship between physiological arousal and self-injurious thoughts and behaviors. [ABSTRACT FROM AUTHOR]

Purpose: The primary purpose of this study was to determine the accuracy of the standard deviation of normal-to-normal intervals (SDNN) to root mean square of successive normal-to-normal interval differences (RMSSD) ratio from 1-min recordings (SDNN:RMSSD1-min) compared to criterion recordings, as well as its relationship to low-frequency-to-high-frequency ratio (LF:HF) at rest and following maximal exercise in a group of collegiate athletes.Method: Twenty athletes participated in the study. Heart rate variability (HRV) data were measured for 5 min before and at 5-10 and 25-30 min following a maximal exercise test. From each 5-min segment, the frequency-domain measures of HF, LF, and LF:HF ratio were analyzed. Time-domain measures of SDNN, RMSSD, and SDNN:RMSSD ratio were also analyzed from each 5-min segment, as well as from randomly selected 1-min recordings.Result: The 1-min values of SDNN, RMSSD, and SDNN:RMSSD provided no significant differences and nearly perfect intra-class correlations (ICCs ranged from 0.97 to 1.00, p < 0.001 for all) to the criterion measures from 5-min recordings. In addition, SDNN, RMSSD, and SDNN:RMSSD from the 1-min segments provided very large to nearly perfect correlations (r values ranged from 0.71 to 0.97, p < 0.001 for all) to LF, HF, and LF:HF, respectively, at each time point.Conclusion: The findings of the study suggest that ultra-shortened time-domain markers may be useful surrogates of the frequency-domain parameters for tracking changes in sympathovagal activity in athletes. [ABSTRACT FROM AUTHOR]

Arterial tone is coordinated among vessel segments to optimize nutrient transport and organ function. Coordinated vasomotor activity is remarkable to observe and depends on stimuli, sparsely generated in tissue, eliciting electrical responses that conduct lengthwise among electrically coupled vascular cells. The conducted response is the focus of this topical review, and in this regard, the authors highlight literature that advances an appreciation of functional significance, cellular mechanisms, and biophysical principles. Of particular note, this review stresses that conduction is enabled by a defined pattern of charge movement along the arterial wall as set by three key parameters (tissue structure, gap junctional resistivity, and ion channel activity). The impact of disease on conduction is carefully discussed, as are potential strategies to restore this key biological response and, along with it, the match of blood flow delivery with tissue energetic demand. [ABSTRACT FROM AUTHOR]

Background: Middle-aged women experience various menopausal symptoms during the menopause. These symptoms can affect their quality of life and health. Several epidemiological studies reported that obesity associates with menopausal symptoms. The aim of this cross-sectional study was to examine the associations between obesity and multiple menopausal symptoms at different stages of menopause in middle-aged Korean women.Methods: The study population included women aged 44-56 years who visited a tertiary referral hospital for medical check-ups between November 2012 and March 2013 and were free from serious illness, could comprehend a questionnaire. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to assess the prevalence of menopausal symptoms. Overweight and obesity were defined as body mass index (BMI) of 23-24.9 and ≥25 kg/m2, respectively.Results: Of the 2204 middle-aged women, 929 met the eligibility criteria. Of these, 533 (57.4%) and 396 (42.6%) were in perimenopause and postmenopause, respectively. In perimenopause, obese women were significantly more likely to have moderate/severe physical symptoms (MENQOL domain score ≥ 5) than normal or overweight women. In postmenopause, obese women were significantly more likely to have moderate/severe vasomotor symptoms. Multiple linear regression with adjustment for confounders showed that relative to normal weight, obesity in perimenopause and postmenopause associated independently with physical symptoms (beta coefficient = 0.35; P = 0.023) and vasomotor symptoms (beta coefficient = 0.68; P = 0.003), respectively. Overweight did not associate with menopausal symptoms. BMI did not associate significantly with psychosocial or sexual symptoms at either stage of menopause.Conclusions: Obese women had more frequent menopausal symptoms than normal or overweight women but the associated menopausal symptom differed depending on the menopausal stage. Further studies are required to confirm this result and identify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Microelectrode array (MEA) based-drug screening with human induced pluripotent stem cell-derived cardiomyocytes (hiPSCM) is a potent pre-clinical assay for efficiently assessing proarrhythmic risks in new candidates. Furthermore, predicting sympathetic modulation of the proarrhythmic side-effects is an important issue. Although we have previously developed an MEA-based co-culture system of rat primary cardiomyocyte and sympathetic neurons (rSNs), it is unclear if this co-culture approach is applicable to develop and investigate sympathetic innervation of hiPSCMs. In this study, we developed a co-culture of rSNs and hiPSCMs on MEA substrate, and assessed functional connections. The inter-beat interval of hiPSCM was significantly shortened by stimulation in SNs depending on frequency and pulse number, indicating functional connections between rSNs and hiPSCM and the dependency of chronotropic effects on rSN activity pattern. These results suggest that our co-culture approach can evaluate sympathetic effects on hiPSCMs and would be a useful tool for assessing sympathetic modulated-cardiotoxicity in human cardiac tissue. [ABSTRACT FROM AUTHOR]

Elevated renal sympathetic nerve activity (RSNA) accompanies a variety of complex disorders, including obstructive sleep apnea, heart failure, and chronic kidney disease. Understanding pathophysiologic renal mechanisms is important for determining why hypertension is both a common sequelae and a predisposing factor of these disorders. The role of the brainstem in regulating RSNA remains incompletely understood. The pedunculopontine tegmentum (PPT) is known for regulating behaviors including alertness, locomotion, and rapid eye movement sleep. Activation of PPT neurons in anesthetized rats was previously found to increase splanchnic sympathetic nerve activity and blood pressure, in addition to altering breathing. The present study is the first investigation of the PPT and its potential role in regulating RSNA. Microinjections of DL-homocysteic acid (DLH) were used to probe the PPT in 100-μm increments in Nembutal-anesthetized rats to identify effective sites, defined as locations where changes in RSNA could be evoked. A total of 239 DLH microinjections were made in 18 rats, which identified 20 effective sites (each confirmed by the ability to evoke a repeatable sympathoexcitatory response). Peak increases in RSNA occurred within 10–20 seconds of PPT activation, with RSNA increasing by 104.5 ± 68.4% (mean ± standard deviation) from baseline. Mean arterial pressure remained significantly elevated for 30 seconds, increasing from 101.6 ± 18.6 mmHg to 135.9 ± 36.4 mmHg. DLH microinjections also increased respiratory rate and minute ventilation. The effective sites were found throughout the rostal-caudal extent of the PPT with most located in the dorsal regions of the nucleus. The majority of PPT locations tested with DLH microinjections did not alter RSNA (179 sites), suggesting that the neurons that confer renal sympathoexcitatory functions comprise a small component of the PPT. The study also underscores the importance of further investigation to determine whether sympathoexcitatory PPT neurons contribute to adverse renal and cardiovascular consequences of diseases such as obstructive sleep apnea and heart failure. [ABSTRACT FROM AUTHOR]

Background: Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries.Objectives: The purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test).Methods: Between 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression.Results: The mean patient age was 62 years, and 42% were male. There were 813 patients (59%) with a pathological ACH test, 33% for CMD and 26% for epicardial vasospasm. A pathological test was more common in females (70% vs. 43%; p < 0.001). In a multivariable logistic regression model the sex difference was statistically significant with a female-male odds ratio for CMD and epicardial vasospasm of 4.2 (95% confidence interval: 3.1 to 5.5; p < 0.001) and 2.3 (95% confidence interval: 1.7 to 3.1; p < 0.001), respectively. Effort-related symptoms, but neither risk factors nor noninvasive stress tests, contributed to predicting a pathological test. Female patients were more sensitive to acetylcholine with vasomotor dysfunction occurring at lower ACH doses compared with male patients.Conclusions: Vasomotor dysfunction is frequent in patients with angina and unobstructed coronaries in a European population. Female patients have a higher prevalence of vasomotor dysfunction (especially CMD) compared with male patients. A pathological ACH test was observed at lower ACH doses in women compared with men. [ABSTRACT FROM AUTHOR]

A small difference in the size of the two pupils is common in healthy individuals, a condition termed benign or physiologic anisocoria (BA). Past research indicates that BA is probably caused by asymmetry in sympathetic nervous system (SNS) function [e.g., Rosenberg (2008). Physiologic anisocoria: A manifestation of a physiologic sympathetic asymmetry.Neuro-Ophthalmology,32, 147–149]. This study is the first to show that BA varies with psychological factors linked to brain asymmetry and autonomic arousal, including gender, attention, and personality. Males exhibited a more directional BA than females, consistent with greater hemispheric lateralization in males. BA also varied with a self-report measure of attentional function, consistent with evidence of hemispheric asymmetry in visuospatial attention networks. Finally, BA varied with personality traits linked to autonomic arousal. Individuals exhibiting higher Meanness and Boldness, and lower Empathy scores tended to show more directional BA. This link between personality traits and BA may be related to brain asymmetries in autonomic arousal and emotion-related processing. If future studies employing direct measures of lateralized brain activity confirm the link between BA and SNS asymmetries, this new metric may prove useful in discovering new relationships between brain organization and psychological function, and how these relationships vary across individuals. [ABSTRACT FROM AUTHOR]

Objective. There is a lack of objective methods for determining the achievement of sympathetic block. This study validates the skin conductance monitor (SCM) as an end point indicator of successful sympathetic blockade as compared with traditional monitors. Methods. This interventional study included 13 patients undergoing 25 lumbar sympathetic blocks to compare time to indication of successful blockade between the SCM indices and traditional measures, clinically visible hyperemia, clinically visible engorgement of veins, subjective skin temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography, within a 30-minute observation period. Differences in the SCM indices were studied pre- and postblock to validate the SCM. Results. SCM showed substantially greater odds of indicating achievement of sympathetic block in the next moment (i.e., hazard rate) compared with all traditional measures (clinically visible hyperemia, clinically visible engorgement of veins, subjective temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography; P ≤ 0.011). SCM indicated successful block for all (100%) procedures, while the traditional measures failed to indicate successful blocks in 16-84% of procedures. The SCM indices were significantly higher in preblock compared with postblock measurements (P < 0.005). Conclusions. This preliminary study suggests that SCM is a more reliable and rapid response indicator of a successful sympathetic blockade when compared with traditional monitors. [ABSTRACT FROM AUTHOR]

Although the human cerebral circulation is richly innervated with sympathetic nerve fibers, the role of sympathetic nerve activity (SNA) on the regulation of cerebral blood flow (CBF) remains debated. Several issues may be responsible for the conflicting conclusions reported in the animal vs. human literature in regards to the sympathetic control of the brain circulation. Furthermore, due to the physiological consequences associated with SNA blockade (e.g. changes in blood pressure and cardiac output), and differences in methodology (e.g. assessment of CBF), interpretation of the role of SNA in CBF regulation in humans is challenging. The goals of this brief review are to provide an overview of the role of neural control in the regulation of CBF, with a focus on SNA and discuss the likely reasons behind the controversial influence of SNA on CBF regulation. A final objective of this article is to critically review the various methods available to measure CBF and highlight their strengths and weaknesses to provide insight in SNA regulation of CBF. [ABSTRACT FROM AUTHOR]

We review the information that has been provided by optical imaging experiments directed at understanding the role and effects of sympathetic nerve activity (SNA) in the functioning of blood vessels. Earlier studies utilized electric field stimulation of nerve terminals (EFS) in isolated arteries and vascular tissues ( ex vivo ) to elicit SNA, but more recently, imaging studies have been conducted in vivo , enabling the study of SNA in truly physiological conditions. Ex vivo : In vascular smooth muscle cells (VSMC) of isolated arteries, the three sympathetic neurotransmitters, norepinephrine (NE), ATP and neuropeptide Y (NPY), elicit or modulate distinct patterns of Ca 2 + signaling, as revealed by confocal imaging of exogenous fluorescent Ca 2 + indicators. Purinergic junctional Ca 2 + transients (jCaTs) arise from Ca 2 + influx during excitatory junction potentials (eJPs), and are associated with the initial neurogenic contraction. Adrenergic Ca 2 + waves and oscillations cause contraction while SNA-induced endothelial Ca 2 + ‘pulsars’ cause relaxation. In vivo : optical biosensor mice, which express genetically encoded Ca 2 + indicators (GECI's) specifically in smooth muscle, combined with non-invasive imaging techniques has enabled imaging SNA-induced Ca 2 + signaling and arterial diameter in vivo . SNA induces Ca 2 + oscillations in intact arteries. [Ca 2 + ] of arterial smooth muscle cells increased in hypertension, in association with increased SNA. High resolution imaging has revealed local sympathetic, neurogenic Ca 2 + signaling within smooth muscle and endothelial cells of the vasculature. The ongoing development of in vivo imaging together with an expanding availability of different biosensor animals promises to enable the further assessment of SNA and its effects in the vasculature of living animals. [ABSTRACT FROM AUTHOR]

Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X7 signal has been shown to activate the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X7 signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin-1β (IL-1β) axis is involved in the process. We explored the relationship between P2X7 receptor (P2X7R) and IL-1β in the heart tissue of lipopolysaccharide (LPS)-primed naive rats. 3′-O-(4-benzoyl) benzoyl adenosine 5′-triphosphate (BzATP), a P2X7R agonist, induced caspase-1 activation and mature IL-1β release, which was further neutralized by a NLRP3 inhibitor (16673-34-0). MI was induced by coronary artery ligation. Following infarction, a marked increase in P2X7R was localized within infiltrated macrophages and observed in parallel with an up-regulation of NLRP3 inflammasome levels and the release of IL-1β in the left ventricle. The administration of A-740003 (a P2X7R antagonist) significantly prevented the NLRP3/IL-1β increase. A-740003 and/or Anakinra (an IL-1 receptor antagonist) significantly reduced macrophage infiltration as well as macrophage-based IL-1β and NGF (nerve growth factor) production and eventually blunted sympathetic hyperinnervation, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP 43). Moreover, the use of Anakinra partly attenuated sympathetic sprouting. This indicated that the effect of P2X7 on neural remodelling was mediated at least partially by IL-1β. The arrhythmia score of programmed electric stimulation was in accordance with the degree of sympathetic hyperinnervation. In vitro studies showed that BzATP up-regulated secretion of nerve growth factor (NGF) in M1 macrophages via IL-1β. Together, these data indicate that P2X7R contributes to neural and cardiac remodelling, at least partly mediated by NLRP3/IL-1β axis. Therapeutic interventions targeting P2X7 signal may be a novel approach to ameliorate arrhythmia following MI. [ABSTRACT FROM AUTHOR]

It has been suggested that novel peptide that is produced from the neuromedin U (NMU) precursor may exist, as this precursor contains multiple consensus sequences for proteolytic processing. Recently, we identified two mature novel peptides comprising 33 and 36 residues in the rat brain, which were designated neuromedin U precursor-related peptide (NURP) 33 and 36. In the present study, we compared the roles of NURP33 and 36 with that of NMU, as neither activates the NMU receptors. Immunoreactivity for NMU and NURPs was widely present in the central nervous system and showed a similar distribution. Intracerebroventricular (icv) injection of NURP33 in rats increased locomotor activity, energy expenditure, heart rate and back surface temperature (BS-T), similarly to NMU or NURP36. NMU treatment reduced food intake, but NURP33 did not. Pretreatment with the β3 blocker, SR59230A, and the cyclooxygenase blocker, indomethacin, inhibited the NURP33- or NMU-induced increase of BS-T. In addition, icv injection of NURP33 or NMU increased the expression of mRNA for cyclooxygenase 2 in the hypothalamus and for uncoupling protein 1 in the brown adipose tissue. These results suggest that although NURP33 and 36 do not activate the NMU receptors, they might exert NMU-like sympathetic nerve action in the brain. [ABSTRACT FROM AUTHOR]

The revolutionary discovery in 1991 by Soltis and Cassis that perivascular adipose tissue (PVAT) has an anti-contractile effect changed how we think about the vasculature. Most experiments on vascular pharmacology begin by removing the fat surrounding vessels. Thus, PVAT was thought to have a minor role in vascular function and its presence was just for structural support. The need to rethink PVAT's role was precipitated by observations that obesity carries a high cardiovascular risk and PVAT dysfunction is associated with obesity. PVAT is a vascular-adipose organ that has intimate connections with the nervous and immune system. A complex world of physiology resides in PVAT, including the presence of an 'adrenergic system' that is able to release, take up and metabolize noradrenaline. Adipocytes, stromal vascular cells and nerves within PVAT contain components that make up this adrenergic system. Some of the great strides in PVAT research came from studying adipose tissue as a whole. Adipose tissue has many roles and participates in regulating energy balance, energy stores, inflammation and thermoregulation. However, PVAT is dissimilar from non-PVAT adipose tissues. PVAT is intimately connected with the vasculature, which is what makes its role in body homeostasis unique. The adrenergic system within PVAT may be an integral link connecting the effects of obesity with the vascular dysfunction observed in obesity-associated hypertension, a condition in which the sympathetic nervous system has a significant role. This review will explore what is known about the adrenergic system in adipose tissue and PVAT, plus the translational importance of these findings.Linked Articles: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) has recently been associated with female sexual function (Stanton, Lorenz, Pulverman, & Meston, 2015). Below-average HRV was identified as a possible risk factor for sexual arousal dysfunction and overall sexual dysfunction in women. Based on this newly established relationship between HRV and female sexual function, the present study examined the effect of autogenic training to increase HRV on acute physiological and subjective sexual arousal in women. Specifically, vaginal pulse amplitude (VPA), an index of genital sexual arousal, and subjective sexual arousal were assessed in 33 sexually functional women, aged 18 to 27, before and after a short session of autogenic training. Autogenic training, a relaxation technique that restores the balance between the activity of the sympathetic and the parasympathetic branches of the autonomic nervous system, has been shown to significantly increase HRV (Miu, Heilman, & Miclea, 2009). After autogenic training, significant increases in both VPA (p <.05) and subjective sexual arousal (p <.005) were observed. Moreover, change in HRV from pre- to postmanipulation significantly moderated changes in subjective sexual arousal (p <.05) when it was measured continuously during the presentation of the erotic stimulus. This cost-effective, easy-to-administer behavioral intervention may have important implications for increasing sexual arousal in women. [ABSTRACT FROM AUTHOR]

Objective:To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. Methods:This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of  ≥145 mm Hg, and/or a daytime diastolic ABPM of  ≥95 mm Hg after witnessed drug intake (including  ≥3 antihypertensive drugs, preferably including a diuretic). Results:The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety. Conclusions:This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension. [ABSTRACT FROM AUTHOR]

Introduction. Greater splanchnic nerve (GSN) is by far the largest of the splanchnic nerves and connects the paravertebral and prevertebral ganglia to transmit the majority of nociceptive information from the viscera. Despite its importance, the immunohistochemical features of the porcine GSN neurons have not yet been examined. Therefore, the aim of the study was to investigate the neurochemistry of the porcine GSN neurons and to compare their neurochemical coding with those of the paravertebral and prevertebral ganglia. Material and methods. Four gilts of Large White Polish breed were examined in this study. Antibodies to tyrosine hydroxylase (TH), dopamine b-hydroxylase (DBH), choline acetyltransferase (ChAT), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin (GAL), methionine-enkephalin (MET), calcitonin gene-related peptide (CGRP), and substance P (SP) were used for immunohistochemical detection of classical neurotransmitters marker enzymes and neuropeptides in neuronal cell bodies of the GSN. Results. Double-labeling immunofluorescence revealed that virtually all GSN neurons exhibited the presence of catecholamine-synthesizing enzymes (TH/DBH-positive) and subpopulations of neurons contained immunoreactivity to NPY, VIP, SOM, GAL and MET. However, CGRP and SP-immunoreactivity were not observed in neuronal somata. Conclusions. Our data strongly suggest that the general immunohistochemical characterization of ganglion cells in the porcine greater splanchnic nerve is similar to that of the prevertebral ganglia (e.g. celiacomesenteric ganglion). [ABSTRACT FROM AUTHOR]

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Objectives. To explore the cardiovascular effects of nightlong repetitive arousals (RA). Methods. Twenty healthy subjects participated in two consecutive sleep studies. The first one was free of intervention and the second study involved repetitive arousals induced by acoustical stimuli. Blood pressure, heart rate variability (HRV), arterial stiffness index (ASI), and serum markers including nitric oxide (NO), endothelin-1 (ET-1), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) were studied. Results. RA led to overnight elevation in diastolic blood pressure (DBP) but not in systolic blood pressure (SBP). Regarding HRV, overnight increase in low frequency power (LF) and low frequency to high frequency ratio (LHR) and decrease in high frequency power (HF) were evident. The relative overnight differences in HF and LHR correlated with the amount of rapid-eye movement (REM) sleep. RA did not cause detectable change in either ASI or serum markers of interest. Conclusions. Nightlong RA alters the sympathovagal modulation significantly and this effect seems to be associated with the amount of REM sleep. Exposure to RA also causes an elevation in postsleep DBP. Disturbance to autonomic nervous system (ANS) may precede endothelial dysfunction and increased arterial stiffness as cardiovascular consequences of RA. [ABSTRACT FROM AUTHOR]

Insomnia is the most prevalent sleep disorder in the United States and has high comorbidity with a number of cardiovascular diseases (CVDs). In the past decade, a number of observational studies have demonstrated an association between insomnia and incident cardiovascular disease (CVD) morbidity and mortality, including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF). Despite some inconsistencies in the literature, likely due to variations in how insomnia is defined and measured, the existing data suggest that insomnia, especially when accompanied by short sleep duration, is associated with increased risk for HTN, CHD and recurrent acute coronary syndrome, and HF. Purported mechanisms likely relate to dysregulation of the hypothalamic-pituitary axis, increased sympathetic nervous system activity, and increased inflammation. This paper reviews the most recent studies of insomnia and CVD and the potential pathophysiological mechanisms underlying this relationship and highlights the need for randomized trials to further elucidate the nature of the relationship between insomnia and CVD. [ABSTRACT FROM AUTHOR]

Quantitative assessment of small-fiber peripheral neuropathy often involves an evaluation of the interaction between the C-fiber sudomotor nerve and local sweat rate (SR). Typically, some sort of quantitative sudomotor axon reflex test (QSART) is performed to aid in diagnosing small-fiber dysfunction. The currently used QSART demonstrates only moderate test-retest reliability and therefore limits its usefulness in tracking small-fiber dysfunction. A new experimental model to examine small C-fiber function in the skin using intradermal electrical stimulation and simultaneous monitoring of SR is proposed. Using intradermal electrical stimulation (1.5 and 2.5 mA) and varying stimulus frequency from 0.2 to 64 Hz, a quantitative relationship between the area under the SR-time curve and log10 stimulus frequency is modeled using a four-parameter logistic equation, providing the following parameters: baseline, plateau, EC50, and Hill slope. The model has good to excellent repeatability within the same day (ICC = 0.98), on different days at the same skin site (ICC = 0.80), and when comparing two different skin sites (ICC = 0.78) with a small bias estimate and the line of identity always lying within the 95% limits of agreement. Atropine sulfate (0.1 mg/ml) blocked 90 ± 5% of the electrically induced sweating. Overall, the model provides control over sudomotor nerve activity and a quantitative assessment of SR. Finally, the ability to reproduce the quantitative stimulus-response curve on different days allows for a robust assessment of the relationship between the activation of a sympathetic C-fiber and local SR. [ABSTRACT FROM AUTHOR]