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Aim: This study assessed the effects of hand‐bathing on sympathetic nervous activity exacerbated by psychological stress. Participants immersed one hand in warm water for 2 min while exposed to noise, and changes in blood flow and skin temperature of the non‐immersed hand were observed. Methods: Twenty‐nine healthy university students aged 20 years or older were randomly assigned to either the hand‐bathing group (n = 14) or the control group (n = 15). After a brief rest in a quiet environment, participants were exposed to noise for 6 min. Those in the hand‐bathing group submerged their left hand in a 40°C thermostatic bath for 2 min, starting 2 min into the noise exposure. The tympanic temperature, blood flow, and skin temperature of the non‐immersed hand were continuously measured, along with blood pressure and subjective evaluations before and after the noise exposure. Results: Both groups experienced a decrease in fingertip skin temperature at the start of the noise exposure, persisting longer in the control group. Conversely, the hand‐bathing group showed increased fingertip skin temperature after 150 s, significantly higher after the noise exposure than the control group (p =.04). Participants in the hand‐bathing group reported significantly increased overall body warmth, thermal comfort, and relaxation during hand‐bathing (p =.007, p =.01, p <.001). Conclusions: The 2‐min hand‐bathing intervention reversed the pronounced vasoconstrictive response induced by noise exposure and elicited heightened sensations of overall body warmth, thermal comfort, and relaxation. Hand‐bathing may mitigate heightened sympathetic nervous activity associated with psychological stress induced by noise exposure. [ABSTRACT FROM AUTHOR]

Frequent extreme cold events in recent years have brought serious threats to outdoor workers and rescuers. Changes in ambient temperature are associated with altered cardiac autonomic function. The study aims to investigate heart rate variability (HRV) and its relationship to other physiological parameters under extreme cold exposures. Twelve males underwent a 30-min preconditioning phase in a neutral environment followed by a 30-min cold exposure (−5, −10, −15, and −20 °C). Time-domain indexes(meanRR, SDNN, RMSSD, and pNN50), frequency domain indexes [Log(HF), Log(LF), and low frequency/high frequency (LF/HF)], parasympathetic nervous system (PNS), and sympathetic nervous system (SNS) were analysed. Results showed all HRV indexes of four cold exposures were significant. The decrease in temperature was accompanied by progressive PNS activation with SNS retraction. SDNN was the most sensitive HRV index and had good linear relationships with blood pressure, pulse, and hand temperature. The results are significant for formulating safety protection strategies for workers in extremely cold environments. Practitioner Summary: This study investigated heart rate variability (HRV) in 12 males during a 30-min cold exposure (−5, −10, −15, and −20 °C). Results showed all HRV indexes of four cold exposures were significant. The decrease in temperature was accompanied by progressive PNS activation with SNS retraction. SDNN was the most sensitive HRV index and had good linear relationships with blood pressure, pulse, and hand temperature. [ABSTRACT FROM AUTHOR]

Background: Diabetic autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), especially in patients with long-term, poorly controlled diabetes. This study investigates the effects of exercise on autonomic nervous system activity in T2DM patients over time. Methods: A literature review using MEDLINE, Embase, Cochrane Library, Scopus, and PubMed identified studies assessed via heart rate variability. Papers were categorized into three groups: immediate effects (within 60 min), short-term effects (2–3 months), and long-term effects (over 4 months). Results: Nine articles with 161 T2DM patients were included in the meta-analysis. RMSSD changes after exercise were −4.3 (p = 0.227), 8.14 (p < 0.001), and 4.17 (p = 0.002) for the immediate, short-term, and long-term groups, respectively. LF/HF ratio changes were 0.21 (p = 0.264), −3.04 (p = 0.102), and −0.05 (p = 0.006) for the respective groups. Meta-regression indicated age, male gender, and exercise duration were associated with increased RMSSD, with coefficients of 2.36 (p = 0.001), 13.76 (p = 0.008), and 1.50 (p = 0.007), respectively. Age positively correlated with the LF/HF ratio, with a coefficient of 0.049 (p = 0.048). Conclusions: Regular exercise (≥3 times per week) for over 2 months increases parasympathetic activity in T2DM patients, while sympathetic activity decreases significantly after 4 months. Further study is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Hypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research. [ABSTRACT FROM AUTHOR]

Background: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects. Methods: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements. Results: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10). Conclusions: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS. [ABSTRACT FROM AUTHOR]

Objectives: Chronic musculoskeletal pain is associated with decreased parasympathetic and increased sympathetic activity in the autonomic nervous system. The objective of this study was to determine the associations between objective measures of heart rate variability (a measure of autonomic nervous system function), actigraphy (a measure of activity and sleep quality), respiration rates, and subjective patient‐reported outcome measures (PROMs) of central sensitization, kinesiophobia, disability, the effect of pain on sleep, and life quality. Methods: Thirty‐eight study subjects were divided into two subgroups, including low symptoms of central sensitization (n = 18) and high symptoms of central sensitization (n = 20), based on patient‐reported scores on the Central Sensitization Inventory (CSI). Heart rate variability (HRV) and actigraphy measurements were carried out simultaneously in 24 h measurement during wakefulness and sleep. Results: A decrease in HRV during the first 2 h of sleep was stronger in the low CSI subgroup compared to the high CSI subgroup. Otherwise, all other HRV and actigraphy parameters and subjective measures of central sensitization, disability, kinesiophobia, the effect of pain on sleep, and quality of life showed only little associations. Discussion: The high CSI subgroup reported significantly more severe symptoms of disability, kinesiophobia, sleep, and quality of life compared to the low CSI subgroup. However, there were only small and nonsignificant trend in increased sympathetic nervous system activity and poorer sleep quality on the high central sensitization subgroup. Moreover, very little differences in respiratory rates were found between the groups. [ABSTRACT FROM AUTHOR]

Background: Myocardial ischemia–reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia–reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons. Methods: Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot. Results: Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect. Conclusion: EA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Orthodontic forces are strongly associated with pain, the primary complaint among patients wearing orthodontic braces. Compared to other side effects of orthodontic treatment, orthodontic pain is often overlooked, with limited clinical management. Orthodontic forces lead to inflammatory responses in the periodontium, which triggers bone remodeling and eventually induces tooth movement. Mechanical forces and subsequent inflammation in the periodontium activate and sensitize periodontal nociceptors and produce orthodontic pain. Nociceptive afferents expressing transient receptor potential vanilloid subtype 1 (TRPV1) play central roles in transducing nociceptive signals, leading to transcriptional changes in the trigeminal ganglia. Nociceptive molecules, such as TRPV1, transient receptor potential ankyrin subtype 1, acid-sensing ion channel 3, and the P2X3 receptor, are believed to mediate orthodontic pain. Neuropeptides such as calcitonin gene-related peptides and substance P can also regulate orthodontic pain. While periodontal nociceptors transmit nociceptive signals to the brain, they are also known to modulate alveolar bone remodeling in periodontitis. Therefore, periodontal nociceptors and nociceptive molecules may contribute to the modulation of orthodontic tooth movement, which currently remains undetermined. Future studies are needed to better understand the fundamental mechanisms underlying neuroskeletal interactions in orthodontics to improve orthodontic treatment by developing novel methods to reduce pain and accelerate orthodontic tooth movement--thereby achieving "big gains with no pain" in clinical orthodontics. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the effects of binaural beat music (BBM) on sleep quality, heart rate variability, and depression in older people with poor sleep quality in a long‐term care institution. Methods: A single‐blind randomized controlled trial design was employed, and 64 older participants with poor sleep quality were recruited from a long‐term care institution in Taiwan. Participants were randomized into the BBM group or control group and received 14 days of intervention. During the intervention period, participants in the experimental group listened to 20 min of Taiwanese Hokkien oldies embedded with BBM once in the morning and afternoon three times a week. Participants in the control group only listened to Taiwanese Hokkien oldies. Questionnaires and heart rate variability analysis were used to assess participants' sleep quality, heart rate variability, and depressive symptoms. Results: Significant improvements were observed in sleep quality, along with an increase in heart rate variability means of heart rate and normal sinus beats, and a decrease in low‐frequency normalized units and depression severity in the BBM group after the intervention. In the control group, effects on sleep quality were inconsistent, heart rate variability showed significant improvements in some autonomic nervous function regulation, and depression severity was significantly decreased. Furthermore, the BBM group showed a significant improvement in sleep quality and a significant reduction in sympathetic nervous activity compared with the control group. Conclusion: This study demonstrates that 14 days of BBM intervention, a non‐invasive intervention, could improve sleep quality and depression in older people with poor sleep quality in long‐term care institutions. Geriatr Gerontol Int 2024; 24: 297–304. [ABSTRACT FROM AUTHOR]

This research aimed to explore the impact of plank exercise training (PET) on respiratory function, body composition, abdominis performance, and autonomic nervous system (ANS). Sixty‐one young adults participated and were divided into a control group (CG, n = 31) and an exercise group (EG, n = 30), wherein PET was administered 3 days per week for 12 weeks. After the experiment, the body composition of the CG deteriorated, whereas that of the EG improved (p < 0.001). The EG exhibited a reduction of ∼34% in the mean maximum displacement and a rise of ∼20% in the mean contraction time of the abdominis. The sit‐up in the EG demonstrated a significant increase of ∼55%. In the EG, there was a substantial increase in peak expiratory force by ∼24% and forced expiratory volume in 1 s by ∼14%, accompanied by a reduction in resting respiratory rate by ∼ −9%. When compared to the CG, these alterations were significant between the two groups (p = 0.001). In the EG, there was a significant decrease in resting heart rate by ∼2%, accompanied by a decrease in sympathetic nervous activity by ∼ −5% and by an increase in parasympathetic nervous activity by ∼5%. When compared to the CG, these alterations were significant between the two groups (p = 0.001). The findings of this study revealed that implementing PET in young adults, while controlling for dietary intake and physical activity, resulted in noteworthy changes in respiratory capacity. These changes were coupled with improvements in body composition, abdominal functions, and the ANS. Highlights: The plank exercise training (PET) resulted in a decrease in body weight, fat mass, body mass index, and waist‐to‐hip ratio, along with an increase in muscle mass over a 12‐week period.The PET led to a decrease in the maximum displacement and an increase in the contraction time, along with an improvement in abdominal muscle endurance.The peak expiratory flow and forced expiratory volume in 1 s exhibited increases as a result of the PET, accompanied by a notable decrease in resting respiratory rate.The PET led to a reduction in resting heart rate, influenced by a decrease in sympathetic nervous activity and an increase in parasympathetic nervous activity. [ABSTRACT FROM AUTHOR]

Acute mental fatigue, characterized by a transient decline in cognitive efficiency during or following prolonged cognitive tasks, can be managed through adaptive effort deployment. In response to mental fatigue, individuals can employ two main behavioral patterns: engaging a compensatory effort to limit performance decrements, or disengaging effort, leading to performance deterioration. This study investigated the behavioral pattern used by participants in mental fatigue conditions. Fifty participants underwent a sequential-task protocol with counterbalanced sessions who took place in two separate sessions: a 30-min incongruent Stroop task (fatiguing session) or a 30-min documentary viewing task (control session), followed by a time-to-exhaustion (TTE) handgrip task at 13 % of maximal voluntary contraction. Psychophysiological measures included the preejection period, heart rate variability, blood pressure, and respiration. Behavioral results showed deteriorated TTE handgrip performance after the Stroop task compared to after the documentary viewing task. During the Stroop task participants were more conservative and prioritized accuracy over speed. Self-reported fatigue was greater after the Stroop task. Psychophysiological data revealed a gradual decrease in sympathetic activity over time in both tasks, with the Stroop task showing a more pronounced decrease. Taken together, these findings suggest a disengagement of effort for a large proportion of participants (49 %) that could be partly attributed to a habituation to the demands of the Stroop task. This study illustrates the interplay of behavioral patterns of effort investment in the context of mental fatigue and underscores the role of disengagement as a dominant response to this phenomenon among healthy participants. • A conservative strategy favoring accuracy was adopted during a cognitive task that induced mental fatigue. • Mental fatigue during a cognitive task leads to a decrease in sympathetic activity with increasing time-on task. • Mental fatigue induced by a 30-min effortful cognitive task impairs the performance in a subsequent endurance physical task. [ABSTRACT FROM AUTHOR]

Competing Interests: None.

There are competing theoretical hypotheses regarding the consequences of early adversity, such as childhood maltreatment, for individuals' autonomic nervous system activity. Research examining potential implications of child maltreatment for sympathetic nervous system activity, specifically, is scarce. In this preregistered study, we examined whether childhood maltreatment history is associated with pregnant adults' sympathetic responses to different stressors. This population is particularly relevant, given potential intergenerational consequences of pregnant individuals' physiological responses to stress. Pregnant women's (N = 162) electrodermal levels were recorded while completing the Trier Social Stress Test (TSST), which elicits social-evaluative threat, and while watching a video of an unfamiliar infant crying, which was intended to activate the attachment system. Pregnant women's retrospective reports of childhood maltreatment were negatively associated with their electrodermal reactivity to the TSST and to the video of the infant crying. Follow-up analyses indicated that these associations were specific to reported experiences of childhood abuse and not childhood neglect. Altogether, these findings indicate that self-reported childhood maltreatment experiences, and childhood abuse in particular, may result in blunted activity of the sympathetic nervous system in response to multiple types of stressors., (© 2024 The Author(s). Developmental Psychobiology published by Wiley Periodicals LLC.)

The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development. Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied, the influence of neural signals, particularly those from the sympathetic nervous system, remains poorly understood. Here, using a mouse mammary gland model, we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary development. Our findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty, adulthood, and pregnancy, accompanied by a reduction in mammary stem cell numbers. Through in vitro three-dimensional culture and in vivo transplantation analyses, we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration, while activation of sympathetic nervous signaling promotes these capacities. Mechanistically, sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the extracellular signal-regulated kinase signaling pathway. Collectively, our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity, offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development., (© The Author(s) (2024). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

BACKGROUND The cold pressor test (CPT), which has long been used to test autonomic functions by causing sympathetic excitation, increases systolic and diastolic blood pressure and heart rate and causes coronary vasodilation within physiological limits in healthy individuals. This study aimed to evaluate internal jugular vein (IJV) flow parameters using the CPT with systolic and diastolic blood pressure and heart rate in 40 healthy volunteers aged 18-40 years. MATERIAL AND METHODS The volunteers' IJV diameter, blood flow peak velocity, and volumetric flow values were recorded. Then, their right hands were immersed in a bucket of cold water maintained at 1°C up to the wrist level. At the end of the first minute (CPT-1), systolic and diastolic blood pressure, heart rhythm, IJV diameter, peak velocity, and volumetric flow measurements were performed again. RESULTS Systolic and diastolic blood pressure values were significantly higher at CPT-1 compared to baseline values (P<0.001, P<0.001). Heart rate and peak velocity values also showed a significant increase at CPT-1 compared to baseline values (P<0.001, P=0.001). While diameter values showed a significant decrease compared to baseline, volumetric flow rate values showed a significant increase at CPT-1 (P=0.003, P<0.001). CONCLUSIONS Sympathetic nervous system activation triggered by CPT increases IJV volumetric flow and flow velocity in healthy young individuals, and sympathetic nervous system activation causes a venoconstrictive effect in the IJV.

The sympathetic nervous system (SNS) consists largely of two different types of components: neurons that release the neurotransmitter norepinephrine (NE, noradrenaline) to modulate homeostasis of the innevrvated effector organ or tissue and adrenal chromaffin cells, which synthesize and secrete the hormone epinephrine (Epi, adrenaline) and some NE into the blood circulation to act at distant organs and tissues that are not directly innervated by the SNS. Like almost every physiological process in the human body, G protein-coupled receptors (GPCRs) tightly modulate both NE release from sympathetic neuronal terminals and catecholamine (CA) secretion from the adrenal medulla. Regulator of G protein Signaling (RGS) proteins, acting as guanosine triphosphatase (GTPase)-activating proteins (GAPs) for the Gα subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins), play a central role in silencing G protein signaling from a plethora of GPCRs. Certain RGS proteins and, in particular, RGS4, have been implicated in regulation of SNS activity and of adrenal chromaffin cell CA secretion. More specifically, recent studies have implicated RGS4 in regulation of NE release from cardiac sympathetic neurons by means of terminating free fatty acid receptor (FFAR)-3 calcium signaling and in regulation of NE and Epi secretion from the adrenal medulla by means of terminating cholinergic calcium signaling in adrenal chromaffin cells. Thus, in this review, we provide an overview of the current literature on the involvement of RGS proteins, with a particular focus on RGS4, in these two processes, i.e., NE release from sympathetic nerve terminals & CA secretion from adrenal chromaffin cells. We also highlight the therapeutic potential of RGS4 pharmacological manipulation for diseases characterized by sympathetic dysfunction or SNS hyperactivity, such as heart failure and hypertension., (© 2024 The Author(s). Published by IMR Press.)

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

In the gastrointestinal tract, nitrergic inhibition of the arteriolar contractility has not been demonstrated. Here, we explored whether neurally-released nitric oxide (NO) inhibits sympathetic vasoconstrictions in the rat rectal arterioles. Changes in sympathetic vasoconstrictions and their nitrergic modulation in rats exposed to water avoidance stress (WAS, 10 days, 1 h per day) were also examined. In rectal submucosal preparations, changes in arteriolar diameter were monitored using video microscopy. In control or sham-treated rats, electrical field stimulation (EFS)-induced sympathetic vasoconstrictions were increased by the neuronal nitric oxide synthase (nNOS) inhibitor L-NPA (1 μM) and diminished by the cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor tadalafil (10 nM). In phenylephrine-constricted, guanethidine-treated arterioles, EFS-induced vasodilatations were inhibited by the calcitonin gene-related peptide (CGRP) receptor antagonist BIBN-4096 (1 μM) but not L-NPA. Perivascular nNOS-immunoreactive nitrergic fibres co-expressing the parasympathetic marker vesicular acetylcholine transporter (VAChT) were intermingled with tyrosine hydroxylase (TH)-immunoreactive sympathetic fibres expressing soluble guanylate cyclase (sGC), a receptor for NO. In WAS rats in which augmented sympathetic vasoconstrictions were developed, L-NPA failed to further increase the vasoconstrictions, while tadalafil-induced inhibition of the vasoconstrictions was attenuated. Phenylephrine- or α,β-methylene ATP-induced vasoconstrictions and acetylcholine-induced vasodilatations were unaltered by WAS. Thus, in arterioles of the rat rectal submucosa, NO released from parasympathetic nerves appears to inhibit sympathetic vasoconstrictions presumably by reducing sympathetic transmitter release. In WAS rats, sympathetic vasoconstrictions are augmented at least partly due to the diminished pre-junctional nitrergic inhibition of transmitter release without changing α-adrenoceptor or P2X-purinoctor mediated vasoconstriction and endothelium-dependent vasodilatation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The impact of physiological stressors on cerebral sympathetic nervous activity (SNA) remains controversial. We hypothesized that cerebral noradrenaline (NA) spillover, an index of cerebral SNA, would not change during both submaximal isometric handgrip (HG) exercise followed by a post-exercise circulatory occlusion (PECO), and supine dynamic cycling exercise. Twelve healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and right internal jugular vein. Right internal jugular vein blood flow was measured using Duplex ultrasound, and tritiated NA was infused through the participants' right superficial forearm vein. Heart rate was recorded via electrocardiogram and blood pressure was monitored using the right radial artery. Total NA spillover increased during HG (P = 0.049), PECO (P = 0.006), and moderate cycling exercise (P = 0.03) compared to rest. Cerebral NA spillover remained unchanged during isometric HG exercise (P = 0.36), PECO after the isometric HG exercise (P = 0.45), and during moderate cycling exercise (P = 0.94) compared to rest. These results indicate that transient increases in blood pressure during acute exercise involving both small and large muscle mass do not engage cerebral SNA in healthy humans. Our findings suggest that cerebral SNA may be non-obligatory for exercise-related cerebrovascular adjustments., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Catheter based renal denervation has recently been FDA approved for the treatment of hypertension. Traditionally, the anti-hypertensive effects of renal denervation have been attributed to the ablation of the efferent sympathetic renal nerves. In recent years the role of the afferent sensory renal nerves in the regulation of blood pressure has received increased attention. In addition, afferent renal denervation is associated with reductions in sympathetic nervous system activity. This suggests that reductions in sympathetic drive to organs other than the kidney may contribute to the non-renal beneficial effects observed in clinical trials of catheter based renal denervation. In this review we will provide an overview of the role of the afferent renal nerves in the regulation of renal function and the development of pathophysiologies, both renal and non-renal. We will also describe the central projections of the afferent renal nerves, to give context to the responses seen following their ablation and activation. Finally, we will discuss the emerging role of the kidney as an interoceptive organ. We will describe the potential role of the kidney in the regulation of interoceptive sensitivity and in this context, speculate on the possible pathological consequences of altered renal function., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Muscle sympathetic nerve responses to sudden sensory stimuli have been elucidated in several studies on young healthy men, showing reproducible interindividual differences ranging from varying degrees of inhibition to no significant change, with very few subjects showing significant excitation. These individual response patterns have been shown to predict the neural response to mental stress and coupled blood pressure responses. The aim of this study was to investigate whether premenopausal healthy women show similar neural and blood pressure responses. Muscle sympathetic nerve recordings from the peroneal nerve were performed in 34 healthy women (mean age 27 ± 8 yr) during sudden sensory stimuli (electrical stimuli to a finger) and 3 min of mental stress (forced arithmetics). After sensory stimuli, 18 women showed varying degrees of inhibition of muscle sympathetic nerve activity (burst amplitude mean reduction 60%, range 34-100%). The remaining 16 showed no inhibition (mean 5%, range -31 to 28%; one subject exhibiting excitation). During 3 min of mental stress, the normalized change in burst incidence for muscle sympathetic nerve activity correlated with the percentage change of muscle sympathetic nerve activity induced by the sensory stimulation protocol (r = 0.64, P = 0.0042). In contrast to men, the neural responses did not predict changes in blood pressure. Thus, premenopausal females show a similar range of individual differences in defense-related muscle sympathetic neural responses as men, but no associated differences in blood pressure responses. Whether these patterns are unchanged after menopause remains to be investigated. NEW & NOTEWORTHY Muscle sympathetic neural responses to sudden sensory stimuli in premenopausal women showed interindividual differences and the distribution of sympathetic responses was similar to that previously found in men. Despite this similarity, the associated differences in transient blood pressure responses seen in men were not found in women. The increased risk of developing hypertension in postmenopausal women warrants an investigation of whether these response patterns are altered after menopause.

Efferent muscle sympathetic nerve activity (MSNA) is under tonic baroreflex control. The arterial baroreflex exerts the strongest influence over medium-sized sympathetic action potential (AP) subpopulations in efferent MSNA recordings. Prior work from multiunit MSNA recordings has shown baroreflex loading selectively abolishes the sympathetic response to hypoxia. The purpose of the study was to examine baroreflex control over different-sized AP clusters and characterize the neural recruitment strategies of sympathetic AP subpopulations with baroreflex and combined baroreflex/chemoreflex (i.e., hypoxia) activation. We loaded the arterial baroreceptors [intravenous phenylephrine (PE)] alone and in combination with systemic hypoxia ([Formula: see text] 80%) in nine healthy young men. We extracted sympathetic APs using the wavelet-based methodology and quantified baroreflex gain for individual AP clusters. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability versus diastolic blood pressure for 10 normalized clusters. Baroreflex loading with phenylephrine decreased MSNA and AP firing compared with baseline (all P < 0.05). However, the phenylephrine-mediated decrease in AP firing was lost with concurrent hypoxia ( P = 0.384). Compared with baseline, baroreflex loading reduced medium-sized AP cluster baroreflex threshold slope (condition P = 0.005) and discharge probability (condition P < 0.0001); these reductions from baseline were maintained during simultaneous hypoxia (both P < 0.05). Present findings indicate a key modulatory role of the baroreceptors on medium-sized APs in blood pressure regulation that withstands competing signals from peripheral chemoreflex activation. NEW & NOTEWORTHY This study provides a novel understanding on baroreflex control of efferent sympathetic nervous system activity during competing stressors: baroreflex loading and peripheral chemoreflex activation. We show chemoreflex activation buffers baroreflex-mediated reductions in sympathetic nervous system activity. More importantly, baroreflex loading reduced baroreflex threshold gain of sympathetic action potential clusters and this reduction withstood chemoreflex activation. These data suggest the arterial baroreflex holds a primary regulatory role over medium-sized sympathetic neurons despite competing chemoreflex signals.

Preclinical models indicate that amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans. Heart rate (HR; electrocardiography), beat-to-beat BP (photoplethysmography), and muscle sympathetic activity (MSNA, microneurography) were continuously measured in 10 young subjects (4 females) during rest across two randomized experimental visits: 1 ) after 3 h of oral administration of placebo (PLA, 10 mg of methylcellulose within a gelatin capsule) and 2 ) after 3 h of oral administration of AMD (10 mg). Visits were separated for at least 48 h. We calculated the standard deviation and other indices of BP variability. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. AMD did not affect HR, BP, and MSNA compared with PLA. Indexes of cardiac autonomic modulation (time- and frequency-domain HR variability) and BP variability were also unchanged after AMD ingestion. Likewise, AMD did not modify the gain of both spontaneous cardiac and sympathetic arterial baroreflex. A single oral dose of AMD does not affect spontaneous arterial baroreflex sensitivity and BP variability in healthy young adults. NEW & NOTEWORTHY Preclinical models indicate that amiloride (AMD), a nonselective antagonist of the acid-sensing ion channels (ASICs), impairs baroreflex sensitivity and perturbs blood pressure regulation. We translated these findings into humans, investigating the impact of acute oral ingestion of AMD on blood pressure variability and spontaneous cardiac and sympathetic baroreflex sensitivity in healthy young humans. In contrast to preclinical evidence, AMD does not impair spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults.

Depressed individuals exhibit altered sensitivity to both positive and negative social contact, and may not reap the same psychological and emotional benefits to socializing as non-depressed individuals. Although depressive symptoms and loneliness predict social withdrawal and decreased pleasure, little is currently understood about immediate affective arousal dynamics during real-time socializing. Using a novel ambulatory protocol that tracked both objective features of affective arousal (electrodermal activity) and subjective valence (self-reported) during college students' social interactions, we evaluated the moderating role of depression and loneliness symptoms on the associations between socializing with others (specifically, with a romantic partner, a close friend, or a group of friends) and the arousal and valence dimensions of affect. Among a racially and ethnically diverse sample of 118 college students (64% African American/Black/Continental African, 20% Latinx, 8% Asian, and 8% White) recruited from a large, predominantly White Midwestern university, those lower in depression and loneliness symptomatology evinced decreased average arousal (Β = -0.10, SE = 0.04, p < .01) when in relaxed and intimate socializing contexts (e.g., with a romantic partner and a close friend), consistent with the idea that these contexts facilitate important opportunities for psychological rest and recovery. Those lower in depression and loneliness symptoms also showed higher average arousal when socializing in the energizing context of being with a group of friends. Overall, the results suggest psychopathology is reflected in patterns of sympathetic arousal when socializing, with more depressed and lonely individuals generally feeling worse while receiving fewer psychophysiological rewards in multiple socializing contexts., (© 2024 Society for Psychophysiological Research.)

Aim: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)-neuregulin 4 (NRG4)-ErbB4 axis, with somatotopic dependence., Materials and Methods: We established a high-fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c-Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B-NRG4-ErbB4 axis was verified by peripheral specific antagonism of ErbB4., Results: ES at the forelimb and abdomen regions significantly up-regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD-induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES., Conclusion: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4-ErbB4 signaling pathway., (© 2024 John Wiley & Sons Ltd.)

An unannounced balance loss during walking, i.e., balance perturbation, is a stressful event, which changes the activity of the sympathetic nervous system (SNS). We examined SNS response to unannounced balance perturbation during walking, simulating real-life condition of balance loss. We asked: do laboratory-induced unannounced balance losses during walking cause a sympathetic response, and-if so-does it habituate after a series of perturbations? Thirty-four young adults underwent a series of six successive unannounced balance perturbations while walking on a treadmill. Sympathetic activity was monitored continuously using electrodermal activity and compared before and immediately after each unannounced perturbation. All perturbations elicited a significant increase of electrodermal activity ( P < 0.001), indicating a phasic increase in the sympathetic drive. The relative phasic increase of electrodermal activity caused by the first perturbation was significantly higher than the last perturbation ( P < 0.05). Three different types of electrodermal activity behavior were observed: steady-level tonic SNS activity, increased SNS activity, and decreased SNS activity. Balance loss during walking triggers phasic SNS response, this response habituates after a series of unannounced balance perturbations. In addition, three distinct patterns of tonic sympathetic activity may imply variations in the ability of the SNS response to habituate across individuals. NEW & NOTEWORTHY Up to date, the literature typically provides information about sympathetic nervous system activity and relatively static balance. We believe that exposing participants to a balance loss during walking, i.e., unexpected perturbation, provides a more ecologically valid situation to measure sympathetic nervous system response; this provides new and vital knowledge that can have a significant impact and understanding of how the SNS responds to a loss of balance in a real-life situation.

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague-Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine-like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin-9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α-NETA, superoxide scavenger tempol or N-acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin-9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin-9 was inhibited by α-NETA. The effects of cNTS microinjection of chemerin-9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK-801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin-9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1-mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin-9-induced responses., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Long-lasting elevated blood pressure (BP), i.e. hypertension, is a major contributor to morbidity and mortality worldwide. As a multifactorial and systemic disease that involves multiple systems, hypertension remains a challenging disease to study. Models of hypertension are a basic source of knowledge to drive and support the discovery of the specific genetic, cellular, and molecular mechanisms underlying essential hypertension, as well as to discover and introduce new possible treatments to lower BP. Animal models of hypertension deliver a huge amount of information but it is important to choose the proper one for our scientific hypothesis. In this review, we discuss the physiological, and biochemical background of rodent models of hypertension through a systems approach and a myriad of mechanisms and pathways involved in blood pressure control. We also pay attention to how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), and immunological system, interfere with each other, and their activity is differentially controlled by sodium delivery, which still remains a pivotal troublemaker.

Purpose: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the information gained by studying non-bursts is unclear. We tested the hypothesis that longer sequences of non-bursts (≥8 cardiac cycles) would be associated with a greater nadir diastolic blood pressure (DBP) and that better popliteal artery function would be associated with an augmented reduction in DBP., Methods: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 39 healthy, adults (age 23.4 ± 5.3 years; 19 females). For each cardiac cycle absent of MSNA bursts, the mean nadir DBP (ΔDBP) during the 12 cardiac cycles following were determined, and separate analyses were conducted for ≥8 or < 8 cardiac cycle sequences. Popliteal artery endothelial-dependent (via flow-mediated dilation; FMD) and endothelial-independent vasodilation (via nitroglycerin-mediated dilation; NMD) were determined., Results: The nadir DBP responses to sequences ≥8 cardiac cycles were larger (-1.40 ± 1.27 mmHg) than sequences <8 (-0.38 ± 0.46 mmHg; p < 0.001). In adjusting for sex and burst frequency (14 ± 8 bursts/min), larger absolute or relative FMD (p < 0.01), but not NMD (p > 0.53) was associated with an augmented nadir DBP. This overall DBP-FMD relationship was similar in sequences ≥8 (p = 0.04-0.05), but not <8 (p > 0.72)., Conclusion: The DBP responses to non-bursts, particularly longer sequences, were inversely associated with popliteal endothelial function, but not vascular smooth muscle sensitivity. This study provides insight into the information gained by quantifying the DBP responses to cardiac cycles absent of MSNA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Type 2 diabetes (T2D) is often accompanied by hypertension, exaggerated blood pressure (BP) responses to sympatho-excitatory stressors, and raised cardiovascular disease risk. Appropriate respiratory-sympathetic coupling and sympathetic transduction to BP are important for short- and longer-term BP control. We tested the hypotheses that respiratory modulation of muscle sympathetic nerve activity (MSNA) and its transduction to BP would be impaired in T2D and associated with higher BP and respiratory-coupled BP variability. Resting MSNA, respiration and beat-to-beat BP were recorded in 20 T2D (49.1 ± 7.4 years; mean ± SD) and 13 healthy control (46.3 ± 9.4 years) participants. MSNA and the transduction of sympathetic bursts (signal-averaging) to mean arterial pressure (MAP) were compared at low and high lung volume phases. The peak MAP response following a sympathetic burst was lower during the high lung volume than low lung volume phase in controls (P = 0.005), whereas it was unchanged with phase in T2D participants (P = 0.522). Respiratory modulation of MSNA was impaired in T2D participants, who had an attenuated reduction in burst incidence from low to the high lung volume phase, versus controls (27.8 ± 38.4% vs. 49.4 ± 24.6%, respectively; P = 0.043). The T2D participants were grouped into unimpaired respiratory modulators (burst incidence modulation median or above) or impaired respiratory modulators (below median). Impaired modulators had higher systolic BP (133 ± 14 vs. 121 ± 11 mmHg, P = 0.046), greater Traube-Hering wave amplitudes (6.3 ± 2.4 vs. 4.6 ± 1.1 mmHg; P = 0.028) and higher BP variability (MAP average real variability, 2.0 ± 0.7 vs. 1.4 ± 0.3, P = 0.033). Respiratory modulation of MSNA and sympathetic transduction to BP are altered in T2D patients and may contribute to their increased hypertension and cardiovascular risk. KEY POINTS: Respiratory-sympathetic coupling and sympathetic transduction to blood pressure (BP) contribute to short- and longer-term BP control. Our understanding of these processes in health and type 2 diabetes (T2D), a condition with high prevalence of hypertension and cardiovascular risk, is incomplete. We found that respiration and sympathetic transduction to BP are coupled in healthy individuals. The mean arterial pressure response to a sympathetic burst was reduced during the high lung volume compared to the low lung volume phase. This coupling was absent in T2D. Respiratory modulation of muscle sympathetic nerve activity (MSNA) is impaired in T2D, with a blunted reduction of MSNA observed during the high lung volume phase. T2D patients with impaired respiratory MSNA modulation had augmented systolic BP, respiratory-related BP excursions (Traube-Hering waves) and BP variability. Abnormal respiratory modulation of MSNA and sympathetic transduction to BP in T2D may contribute to altered blood pressure control and cardiovascular risk in this population., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The purpose of this systematic review and meta-analysis was to examine the effects of exercise training on muscle sympathetic nerve activity (MSNA) in humans. Studies included exercise interventions [randomized controlled trials (RCTs), nonrandomized controlled trials (non-RCTs), or pre-to-post intervention] that reported on adults (≥18 yr) where MSNA was directly assessed using microneurography, and relevant outcomes were assessed [MSNA (total activity, burst frequency, burst incidence, amplitude), heart rate, blood pressure (systolic blood pressure, diastolic blood pressure, or mean blood pressure), and aerobic capacity (maximal or peak oxygen consumption)]. Forty intervention studies ( n = 1,253 individuals) were included. RCTs of exercise compared with no exercise illustrated that those randomized to the exercise intervention had a significant reduction in MSNA burst frequency and incidence compared with controls. This reduction in burst frequency was not different between individuals with cardiovascular disease compared with those without. However, the reduction in burst incidence was greater in those with cardiovascular disease [9 RCTs studies, n = 234, mean difference (MD) -21.08 bursts/100 hbs; 95% confidence interval (CI) -16.51, -25.66; I 2 = 63%] compared with those without (6 RCTs, n = 192, MD -10.92 bursts/100 hbs; 95% CI -4.12, -17.73; I 2 = 76%). Meta-regression analyses demonstrated a dose-response relationship where individuals with higher burst frequency and incidence preintervention had a greater reduction in values post-intervention. These findings suggest that exercise training reduces muscle sympathetic nerve activity, which may be valuable for improving cardiovascular health. NEW & NOTEWORTHY This systematic review and meta-analysis suggests exercise training reduces muscle sympathetic nerve activity (MSNA), which may be valuable for improving cardiovascular health. The reduction in burst incidence was greater among individuals with cardiovascular disease when compared with those without; exercise training may be particularly beneficial for individuals with cardiovascular disease. Meta-regression analyses demonstrated a dose-response relationship, where individuals with higher sympathetic activity preintervention had greater reductions in sympathetic activity post-intervention.

The present study investigated the impact of central α 2 -adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α 2 -adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg -1 ; maintenance infusion of 0.1-0.5 µg kg h -1 ) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats -1 , P = 0.003) most strongly for medium-sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats -1 ; P < 0.001). Dexmedetomidine progressively de-recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de-recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats -1 , P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ -0.09 ± 0.07 to Δ -0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium-sized APs (normalized cluster 2: -6.0 ± 5 to -1.6 ± 2 % mmHg -1 ; P = 0.008). These data suggest that α 2 -adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. KEY POINTS: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α 2 -adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α 2 -adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Short and insufficient sleep are prevalent and associated with cardiovascular disease, with the sympathetic nervous system as a suspected mediator. The purpose of the present study was to investigate the association between objective, actigraphy-based total sleep time (TST), sleep efficiency (SE), and cardiovascular and sympathetic regulation in healthy adults. We hypothesized that short TST and low SE would be associated with elevated resting blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA). Participants included 94 individuals [46 males, 48 females, age: 30 ± 15 yr, body mass index (BMI): 26 ± 4 kg/m 2 ]. All participants underwent at least 7 days of at-home, wristwatch actigraphy monitoring (avg: 10 ± 3 days). Seated blood pressures were assessed using brachial blood pressure measurements, followed by a 10-minute supine autonomic testing session consisting of continuous HR (electrocardiogram), beat-by-beat blood pressure (finger plethysmograph), and MSNA (microneurography) monitoring. Partial correlations were used to determine the relationship between sleep and cardiovascular parameters while accounting for the influence of age, sex, and BMI. TST was not associated with MAP ( R = -0.105, P = 0.321), HR ( R = 0.093, P = 0.383), or MSNA burst frequency (BF; R = -0.168, P = 0.112) and burst incidence (BI; R = -0.162, P = 0.124). Similarly, SE was not associated with MAP ( R = -0.088, P = 0.408), HR ( R = -0.118, P = 0.263), MSNA BF ( R = 0.038, P = 0.723), or MSNA BI ( R = 0.079, P = 0.459). In contrast to recent preliminary findings, our results do not support a significant association between actigraphy-based sleep duration or efficiency and measures of resting blood pressure, heart rate, and MSNA. NEW & NOTEWORTHY The present study investigated the independent association between actigraphy-based sleep duration, efficiency, and measures of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) in adult males and females. Contrary to our hypothesis, the findings do not support an independent association between habitual sleep and cardiovascular or sympathetic neural activity. However, these findings do not preclude a potential association between these parameters in populations with sleep disorders and/or cardiovascular disease.

The sympathetic nervous system is critical for regulating blood pressure (BP) via the arterial baroreflex and sympathetic transduction in the peripheral vasculature. These mechanisms interact, and both may be altered with aging and impacted by menopause. Although age-related decreases in sympathetic transduction have been demonstrated in women, it remains unclear whether sympathetic baroreflex sensitivity (BRS) is impaired in postmenopausal women (POST). We tested the hypothesis that sympathetic BRS would be enhanced in POST compared with premenopausal women (PRE). We examined beat-by-beat BP and muscle sympathetic nerve activity (MSNA) in 19 PRE (22 ± 2 yr, 22 ± 3 kg/m 2 ) and 12 POST (57 ± 5 yr, 24 ± 2 kg/m 2 ) during 10 min of rest. Spontaneous sympathetic BRS was quantified as the slope of a linear regression between MSNA burst incidence and diastolic BP. Sympathetic transduction to mean arterial pressure (MAP) for the 10 cardiac cycles following spontaneous MSNA bursts was assessed via signal averaging method. Resting MAP was similar (PRE: 82 ± 8 vs. POST: 85 ± 8 mmHg, P = 0.43), whereas resting MSNA was elevated in POST (PRE: 10 ± 6 vs. POST: 45 ± 16 bursts/100 heart beats, P < 0.0001). Spontaneous sympathetic BRS was enhanced in POST (PRE: -2.0 ± 1.2 vs. POST: -5.2 ± 1.9 bursts/beat/mmHg, P < 0.0005). Sympathetic transduction to MAP was attenuated in POST (time: P < 0.001, group: P < 0.001, interaction: P < 0.01). These data suggest that sympathetic BRS may be enhanced in POST. Consistent with recent hypotheses, enhanced sensitivity of the arterial baroreflex's neural arc may signify a compensatory response to reduced efficiency of the peripheral arterial baroreflex arc (i.e., sympathetic transduction) to preserve BP buffering capacity. NEW & NOTEWORTHY Studies examining sympathetic baroreflex function with aging remain equivocal, with some studies showing an increase, decrease, or no change in sympathetic baroreflex sensitivity (BRS) in older adults compared with younger adults. With aging, women experience unique physiological changes due to menopause that influence autonomic function. For the first time, we show that postmenopausal women exhibit a greater sympathetic BRS compared with young premenopausal women.

Body posture and biological sex exhibit independent effects on the sympathetic neural responses to dynamic exercise. However, the neural mechanisms (e.g., baroreflex) by which posture impacts sympathetic outflow during rhythmic muscular contractions, and whether biological sex affects posture-mediated changes in efferent sympathetic nerve traffic during exercise, remain unknown. Thus, we tested the hypotheses that increases in muscle sympathetic nerve activity (MSNA) would be greater during upright compared with supine rhythmic handgrip (RHG) exercise, and that females would demonstrate smaller increases in MSNA during upright RHG exercise than males. Twenty young (30 [6] yr; means [SD]) individuals (9 males, 11 females) underwent 6 min of supine and upright (head-up tilt 45°) RHG exercise at 40% maximal voluntary contraction with continuous measurements of MSNA (microneurography), blood pressure (photoplethysmography), and heart rate (electrocardiogram). In the pooled group, absolute MSNA burst frequency ( P < 0.001), amplitude ( P = 0.009), and total MSNA ( P < 0.001) were higher during upright compared with supine RHG exercise. However, body posture did not impact the peak change in MSNA during RHG exercise (range: P = 0.063-0.495). Spontaneous sympathetic baroreflex gain decreased from rest to RHG exercise ( P = 0.006) and was not impacted by posture ( P = 0.347). During upright RHG exercise, males demonstrated larger increases in MSNA burst amplitude ( P = 0.002) and total MSNA ( P = 0.001) compared with females, which coincided with greater reductions in sympathetic baroreflex gain among males ( P = 0.004). Collectively, these data indicate that acute attenuation of baroreflex-mediated sympathoinhibition permits increases in MSNA during RHG exercise and that males exhibit a greater reserve for efferent sympathetic neural recruitment during orthostasis than females. NEW & NOTEWORTHY The impact of posture and sex on cardiovascular control during rhythmic handgrip (RHG) exercise is unknown. We show that increases in muscle sympathetic nerve activity (MSNA) during RHG are partly mediated by a reduction in sympathetic baroreflex gain. In addition, males demonstrate larger increases in total MSNA during upright RHG than females. These data indicate that the baroreflex partly mediates increases in MSNA during RHG and that males have a greater sympathetic vasoconstrictor reserve than females.

Background: Para-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP)., Method: 10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded., Results: Overall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05)., Conclusion: tVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is clear evidence that the sympathetic nervous system (SNS) mediates bone metabolism. Histological studies show abundant SNS innervation of the periosteum and bone marrow-these nerves consist of noradrenergic fibers that immunostain for tyrosine hydroxylase, dopamine beta-hydroxylase, or neuropeptide Y. Nonetheless, the brain sites that send efferent SNS outflow to the bone have not yet been characterized. Using pseudorabies (PRV) viral transneuronal tracing, we report, for the first time, the identification of central SNS outflow sites that innervate bone. We find that the central SNS outflow to bone originates from 87 brain nuclei, sub-nuclei, and regions of six brain divisions, namely the midbrain and pons, hypothalamus, hindbrain medulla, forebrain, cerebral cortex, and thalamus. We also find that certain sites, such as the raphe magnus (RMg) of the medulla and periaqueductal gray (PAG) of the midbrain, display greater degrees of PRV152 infection, suggesting that there is considerable site-specific variation in the levels of central SNS outflow to the bone. This comprehensive compendium illustrating the central coding and control of SNS efferent signals to bone should allow for a greater understanding of the neural regulation of bone metabolism, and importantly and of clinical relevance, mechanisms for central bone pain., Competing Interests: VR, DL, KG, SK Reviewing editor, eLife, AG, RW, FK, LC, HK, OM, OB, SS No competing interests declared, TY Senior editor, eLife, MZ consults for Gershon Lehmann, Guidepoint and Coleman groups, (© 2024, Ryu et al.)

Emotion regulation (ER) is a multifaceted construct, involving behavioral, cognitive, and physiological processes. Although autonomic coordination is theorized to play a crucial role in adaptive functioning, few studies have examined how different individual and contextual factors together may contribute to such coordination. This study examined the joint influences of narrative processing and emotional negativity/lability (N/L) traits on the coordination of the sympathetic and parasympathetic nervous systems in a sample of 112 children, ages 8-12 years (M age  = 10.15 years, SD = 1.33). Children completed a stress-induction task followed by an interview about the task. Children's trait-level N/L was assessed via parent-report on the Emotion Regulation Checklist. Narrative processing was assessed and coded based on children's narrative accounts of the event (i.e., causal coherence, overall emotional tone). Indexes of sympathetic (skin conductance response, SCR) and parasympathetic (respiratory sinus arrhythmia, RSA) functioning were derived from physiological data obtained during the interview. Results revealed that children's trait-level N/L and narrative processing of the stressful event interacted to predict the RSA-SCR correlation. Specifically, children who were high on either N/L or narrative causal coherence, but not both, demonstrated significant RSA-SCR correlation. Similarly, children with high N/L and negative-to-neutral narratives, as well as those with low N/L and neutral-to-positive narratives, exhibited significant RSA-SCR correlation. This work provides empirical evidence that narrative processing and trait N/L, together with RSA-SCR correlation, work in tandem to regulate emotional arousal., (© 2024 Society for Psychophysiological Research.)

Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males ( n = 9) and females ( n = 7) completed two experimental days. On day 1 , participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency ( P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task ( P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation. NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

During times of stress, we look to close others for support. Social support conversations are critical for relationship maintenance and well-being. Yet, certain ways of talking about problems-such as co-ruminating-can exacerbate stress. Since social support and co-rumination are both dyadic processes, it is important to examine physiological responses during these conversations in a dyadic manner. Little research has examined physiological synchrony of the sympathetic nervous system (SNS) during social support conversations or co-ruminative conversations. The current research capitalizes on an experimental manipulation of co-rumination using a sample of close friends (147 dyads) and romantic partners (113 dyads) to examine physiological covariation in the context of support. Across both samples, dyads exhibited significant physiological covariation in pre-ejection period reactivity (PEP). Contrary to our hypothesis, dyads in the co-rumination condition did not show more covariation. Close friend dyads did, however, exhibit more covariation as compared to romantic dyads. We also found significant variability in physiological covariation across dyads, with a minority of dyads exhibiting negative covariation of PEP reactivity. The homogeneity of the samples limits the generalizability of the findings and highlights the need for more diverse samples in future work. These findings underline the need for further exploration into the mechanisms that contribute to distinct patterns of physiological synchrony, the conditions in which negative synchrony occurs, and what predicts especially strong positive synchrony. This work extends our understanding of physiological synchrony of the sympathetic nervous system during support conversations and emphasizes the importance of considering heterogeneity in physiological processes., (© 2024 Society for Psychophysiological Research.)

Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardiovagal arms. Since sympathetic postganglionic neurons also innervate the left ventricle (LV), it is often assumed that the LV produces a sympathetically mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine 1 ) whether LV contractility increases in response to baroreceptor unloading and 2 ) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system. Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/d t max )], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60 s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol + atropine. Under control conditions, PAdP/d t max increased during baroreceptor unloading (26 ± 6 vs. 31 ± 9 mmHg·s -1 ·μL -1 , P = 0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11 ± 2 vs. 12 ± 2, P = 0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26 ± 6 vs. 31 ± 9, P = 0.019). During combined esmolol and atropine, there was a small increase in contractility versus control (13 ± 3 vs. 15 ± 4, P = 0.046). Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated. NEW & NOTEWORTHY This study empirically demonstrates a sympathetically mediated increase in LV contractility in response to baroreceptor unloading using a load-independent index of cardiac contractility in the anesthetized rat.

The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older females (mean ± SD, 70 ± 6 yr) and 11 younger females (20 ± 1 yr) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0°), and their lower limbs were passively lifted at 10°, 20°, 30°, and 40° (3 min at each angle). Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. The central venous pressure was estimated based on peripheral venous pressure (eCVP), which was monitored using a cannula in the right large antecubital vein. Baseline MSNA was higher in older females than in younger females. MSNA burst frequency (BF) decreased during the PLR test in both older and younger females, but the magnitude of the decrease in MSNA BF was smaller in older females than in younger females (older, -3.5 ± 1.5 vs. younger, -6.3 ± 1.5 bursts/min at 40° from baseline, P = 0.014). The eCVP increased during the PLR in both groups, and there was no difference in the changes in eCVP between the two groups (older, +1.07 ± 0.37 vs. younger, +1.12 ± 0.33 mmHg at 40° from baseline, P = 0.941). These results suggest that inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age in females. NEW & NOTEWORTHY There were no available data concerning the effect of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. The magnitude of the decrease in muscle sympathetic nerve activity during passive leg raising (10°-40°) was smaller in older females than in young females. In females, inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age.

Na V 1.7 plays a crucial role in inducing and conducting action potentials in pain-transducing sensory nociceptor fibres, suggesting that Na V 1.7 blockers could be effective non-opioid analgesics. While SCN9A is expressed in both sensory and autonomic neurons, its functional role in the autonomic system remains less established. Our single neuron rt-PCR analysis revealed that 82% of sympathetic neurons isolated from guinea-pig stellate ganglia expressed Na V 1.7 mRNA, with Na V 1.3 being the only other tetrodotoxin-sensitive channel expressed in approximately 50% of neurons. We investigated the role of Na V 1.7 in conducting action potentials in postganglionic sympathetic nerves and in the sympathetic adrenergic contractions of blood vessels using selective Na V 1.7 inhibitors. Two highly selective Na V 1.7 blockers, GNE8493 and PF 05089771, significantly inhibited postganglionic compound action potentials by approximately 70% (P < 0.01), with residual activity being blocked by the Na V 1.3 inhibitor, ICA 121431. Electrical field stimulation (EFS) induced rapid contractions in guinea-pig isolated aorta, pulmonary arteries, and human isolated pulmonary arteries via stimulation of intrinsic nerves, which were inhibited by prazosin or the Na V 1 blocker tetrodotoxin. Our results demonstrated that blocking Na V 1.7 with GNE8493, PF 05089771, or ST2262 abolished or strongly inhibited sympathetic adrenergic responses in guinea-pigs and human vascular smooth muscle. These findings support the hypothesis that pharmacologically inhibiting Na V 1.7 could potentially reduce sympathetic and parasympathetic function in specific vascular beds and airways. KEY POINTS: 82% of sympathetic neurons isolated from the stellate ganglion predominantly express Na V 1.7 mRNA. Na V 1.7 blockers inhibit action potential conduction in postganglionic sympathetic nerves. Na V 1.7 blockade substantially inhibits sympathetic nerve-mediated adrenergic contractions in human and guinea-pig blood vessels. Pharmacologically blocking Na V 1.7 profoundly affects sympathetic and parasympathetic responses in addition to sensory fibres, prompting exploration into the broader physiological consequences of Na V 1.7 mutations on autonomic nerve activity., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement, sometimes with an accompanying feeling of nausea. We recently showed that transcranial alternating current stimulation (tACS) of the dorsolateral prefrontal cortex (dlPFC) also modulates MSNA, but does not generate any perceptions. Here, we tested the hypothesis that when the two stimuli are given concurrently, the modulation of MSNA would be additive. MSNA was recorded from 11 awake participants via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve at the fibular head. Sinusoidal stimuli (± 2 mA, 0.08 Hz, 100 cycles) were applied in randomised order as follows: (i) tACS of the dlPFC at electroencephalogram (EEG) site F4 and referenced to the nasion; (ii) bilateral sGVS applied to the vestibular apparatuses via the mastoid processes; and (iii) tACS and sGVS together. Previously obtained data from 12 participants supplemented the data for stimulation protocols (i) and (ii). Cross-correlation analysis revealed that each stimulation protocol caused significant modulation of MSNA (modulation index (paired data): 35.2 ± 19.4% for sGVS; 27.8 ± 15.2% for tACS), but there were no additive effects when tACS and sGVS were delivered concurrently (32.1 ± 18.5%). This implies that the vestibulosympathetic reflexes are attenuated with concurrent dlPFC stimulation. These results suggest that the dlPFC is capable of blocking the processing of vestibular inputs through the brainstem and, hence, the generation of vestibulosympathetic reflexes., (© 2024. The Author(s).)