Autonomic Neuroscience[JOURNAL]
Sun
200 papers
Novel role for purinergic 2× subtype 4 (P2X4) receptors in the exercise pressor reflex and mechanoreflex: Effect of heart failure.
Butenas ALE, Baranczuk AM, Carroll RJ … +5 more , Parr SK, Ade CJ, Hageman KS, Musch TI, Copp SW
Auton Neurosci · 2025 Aug · PMID 40233602 · Full text
We investigated the role played by ATP-sensitive purinergic 2 × 4 (P2X4) receptors on the sensory endings of thin fibre muscle afferents in exercise pressor reflex and mechanoreflex activation in healthy/SHAM rats and ra...
We investigated the role played by ATP-sensitive purinergic 2 × 4 (P2X4) receptors on the sensory endings of thin fibre muscle afferents in exercise pressor reflex and mechanoreflex activation in healthy/SHAM rats and rats with heart failure with reduced ejection fraction (HF-rEF). We hypothesized that infusion of the P2X4 receptor antagonist 5-BDBD (8 μg) into the hindlimb arterial supply would reduce the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to 30s of electrically-induced hindlimb skeletal muscle contraction (model of exercise pressor reflex activation) and 30s of hindlimb skeletal muscle stretch (model of mechanoreflex activation) in decerebrate, unanesthetized HF-rEF rats but not SHAM rats. Ejection fraction was significantly lower in HF-rEF (46 ± 3 %) compared to SHAM (83 ± 2 %; P < 0.001) rats. In SHAM rats, P2X4 receptor blockade had no effect on the pressor response to hindlimb muscle contraction (n = 8) or the pressor and RSNA response to muscle stretch (n = 4). However, in SHAM rats we found that P2X4 receptor blockade significantly reduced the RSNA response to muscle contraction. In HF-rEF rats, P2X4 receptor blockade reduced the pressor and RSNA response to hindlimb muscle contraction (n = 7) as well as the pressor, but not the RNSA, response to hindlimb muscle stretch (n = 8). Collectively, the data suggest that P2X4 receptors on thin fibre muscle afferent sensory endings play a role in the evoking the exercise pressor reflex in healthy subjects that is limited to RSNA, and that in HF-rEF this expands to a significant role in mechanoreflex and exercise pressor reflex-mediated blood pressure control.
Carotid chemoreceptor inhibition improves exercise tolerance in participants with elevated carotid chemosensitivity: A secondary analysis.
Collins SÉ, Phillips DB, Stickland MK
Auton Neurosci · 2025 Aug · PMID 40220511 · Publisher ↗
RATIONALE: Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are characterized by exaggerated carotid chemoreceptor (CC) sensitivity and exercise intolerance. We tested the hypothesis that part...
RATIONALE: Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are characterized by exaggerated carotid chemoreceptor (CC) sensitivity and exercise intolerance. We tested the hypothesis that participants with elevated CC sensitivity would have the greatest improvement in exercise tolerance with CC inhibition, secondary to increased vascular conductance, and lower ventilatory requirements, dyspnea and leg discomfort. METHODS: Data from healthy controls, and patients with CHF or COPD were included in this secondary analysis of results from 2 randomized placebo-controlled double-blind crossover trials. Assessments included pulmonary function, incremental cardiopulmonary exercise test, and basal CC sensitivity assessment. High CC sensitivity was defined as either a stepwise hypoxic ventilatory response (HVR) or transient HVR greater than one SD above the mean in healthy controls. Participants received 2 μg/kg/min dopamine or placebo infusions (randomized) during 2 separate constant work-rate exercise tests to examine exercise endurance time (EET) and cardiopulmonary responses. RESULTS: Among 33 adults, 17 were categorized to normal HVR (11 controls/3 COPD/3 CHF), and 16 to high HVR (1 control/7 COPD/8 CHF). Participants with high HVR experienced significant dopamine-induced improvements in EET (p = 0.011), and reduced leg discomfort at the 4-min isotime (p = 0.024). Those with improved vascular conductance and leg discomfort had the greatest improvements in EET (p = 0.042 and p = 0.021, respectively). CONCLUSIONS: CC inhibition with dopamine in participants with high HVR was associated with improvement in EET. These findings suggest that high HVR is related to exercise limitation, and that improvement in EET is associated with a CC-mediated increase in vascular conductance and leg discomfort.
The effects of rhythmic handgrip exercise on muscle sympathetic nerve activity: A systematic review and meta-analysis.
Maier LE, Meyer SE, Deprato A … +4 more , Busch S, Sivak A, Davenport MH, Steinback CD
Auton Neurosci · 2025 Jun · PMID 40203748 · Publisher ↗
This systematic review and meta-analysis was conducted to quantify the sympathetic response to rhythmic handgrip exercise in healthy and diseased populations. Structured searches of databases were performed until June 12...
This systematic review and meta-analysis was conducted to quantify the sympathetic response to rhythmic handgrip exercise in healthy and diseased populations. Structured searches of databases were performed until June 12, 2024. We included all primary studies (other than systematic reviews and meta-analyses), and inclusion criteria were: population (all populations); intervention (rhythmic handgrip); comparator (baseline); and outcome (MSNA, BP, HR). Forty-nine studies (n = 930) were included. Burst frequency was elevated by 6.1 bursts/min during rhythmic handgrip (95 % CI, 4.52, 7.63; I = 53 %; p < 0.00001) across all populations. Similarly, burst incidence and total activity showed significant increases during handgrip (BI: MD, 3.0 bursts/100 hbs; 95 % CI, 0.11, 5.85; I = 0 %; p = 0.04; TA: MD, 49.4 a.u.; 95 % CI, 36.56, 62.20; I = 86 %; p < 0.00001). Subgroup analyses found greater responses in MSNA during rhythmic handgrip in healthy individuals compared to cardiovascular diseases and other conditions. Specifically, the change in burst frequency during handgrip (p = 0.0009) and total activity during handgrip (p < 0.00001) suggest a blunted sympathetic response to rhythmic handgrip in diseased populations. Meta-regression analyses in healthy populations found no relationship between the volume of handgrip applied with the associated change in sympathetic activity; however, there was a significant positive relationship between both the change in heart rate (slope = 0.131; adjusted R = 0.2773; p = 0.002) and the change in mean blood pressure (slope = 0.163; adjusted R = 0.3594; p < 0.001) with handgrip volume. An increase in MSNA is observed during rhythmic handgrip despite ranging protocols, populations, and co-interventions. These results suggest exercise is a unique stressor and challenges the understanding of general sympathetic hyperactivity in diseased populations.
Autonomic control of blood pressure in women: The roles of hypertension and aging.
Akins JD, Washio T, Fu Q
Auton Neurosci · 2025 Aug · PMID 40188759 · Full text
Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, with implications in women's health across the lifespan. Of note, autonomic nervous system imbalances have been linked to the deve...
Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, with implications in women's health across the lifespan. Of note, autonomic nervous system imbalances have been linked to the development of hypertension and are present with natural aging and various conditions unique to women (e.g., menopause, hypertensive disorders of pregnancy, polycystic ovary syndrome). As such, this article reviews the critical changes in the sympathetic and parasympathetic nervous systems that occur in women and may contribute to the development of hypertension. Special focus is paid to the regulating pathways across the baroreflex arc, including baroreflex sensitivity, efferent sympathetic outflow, and peripheral sympathetic transduction, at rest and during various physiological stressors. To this point, aging women experience increasing sympathetic outflow, blunted sympathetic transduction, and reduced cardiovagal baroreflex sensitivity, which may be further potentiated by the presence of hypertension. Additionally, this review applies some clinical perspective to the physiological findings in order to identify potential therapeutic pathways. The information gathered in this review has important implications for future research into women's autonomic blood pressure regulation and its impact on the genesis of hypertension.
The influence of sleep on autonomic nervous system regulation in women across the lifespan.
Bigalke JA, Carter JR
Auton Neurosci · 2025 Aug · PMID 40188758 · Publisher ↗
Sleep and autonomic regulation are closely related processes which incur significant influence on health and wellbeing in women across the lifespan. Aging in women is associated with increases in cardiovascular risk thro...
Sleep and autonomic regulation are closely related processes which incur significant influence on health and wellbeing in women across the lifespan. Aging in women is associated with increases in cardiovascular risk through greater sympathetic predominance compared to premenopausal women, as well as reductions in sleep quality and quantity. Women remain an understudied population with regards to sleep, autonomic function, and cardiovascular risk. Understanding the interplay between sleep and autonomic function across the lifespan of women is crucial to improve subsequent lifelong health outcomes. The present review integrates knowledge that has accrued regarding experimental sleep deprivation, restriction, and chronic sleep disturbance and their respective impacts on autonomic regulation at various life stages in women. The review focuses on high-fidelity measures of sympathetic regulation (i.e., microneurography), as aging in women is associated with a disproportionate increase in sympathetic activity compared to men. Evidence summarized within this review delineates a significant impact of sleep processes on autonomic function in women across the lifespan. However, there remain substantial gaps in our knowledge of this interplay between sleep processes and autonomic regulation of cardiovascular control in women. There is a need for further research efforts to disentangle the complexity associated with sleep and autonomic regulation in women at all life stages. Efforts in this area will improve our understanding of women's health and factors such as sleep and sleep disturbance which precipitate lifelong health and chronic cardiovascular risk.
Orthostatic cardiovascular responses to postural sway and discreet counterpressure maneuvers.
Williams EL, Lando J, Lucci VM … +5 more , Hockin BCD, Elabd K, Robinovitch SN, Parsons IT, Claydon VE
Auton Neurosci · 2025 Aug · PMID 40187276 · Publisher ↗
Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingl...
Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingly, we aimed to evaluate a series of discreet, accessible movements as novel preventative CPM. We tested 26 healthy adults (12 female) aged 28.9 ± 1.2 years. Participants performed a baseline stand (BL), followed by three randomized CPM trials (exaggerated anteroposterior sway, AP; toe clenching, TC; gluteal muscle clenching, GC). Non-invasive beat-to-beat systolic arterial pressure (SAP), heart rate, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), mean middle cerebral artery blood velocity (mMCAv), and total path length moved (TPL) were measured. Muscularity was assessed using bioelectrical impedance. All discreet CPM augmented orthostatic SV (p < 0.001) and CO (p < 0.001), while reducing TPR (p < 0.001). SAP increased during AP (p < 0.001) and GC (p < 0.001), but not TC. GC responses were unstable, with increased standard deviation of SAP (p = 0.002) and SV (p = 0.022) that may predispose syncope. Only AP improved mMCAv (p = 0.005) and sympathovagal balance (p < 0.001). Responses were largest in those with greater initial cardiovascular instability (p < 0.003), larger leg muscle mass (p < 0.02), and where TPL was greater (p < 0.002). These novel CPM hold clinical potential for the prevention of orthostatic syncope and presyncope, while addressing real-world patient-reported barriers to CPM. Exaggerated AP sway was most robust and stable at improving orthostatic hemodynamics in healthy controls, with reduced reliance on sympathetic baroreflex-mediated vasoconstriction during enhanced muscle pumping activity. Accordingly, AP shows the most promise as a simple and discrete CPM.
Cardiovascular and sympathetic neural responses during acute vagus nerve stimulation and subsequent static handgrip exercise in healthy adults.
Washio T, Akins JD, Hissen SL … +3 more , Geib AK, Robles SA, Fu Q
Auton Neurosci · 2025 Jun · PMID 40168812 · Publisher ↗
PURPOSE: This study aimed to investigate cardiovascular and sympathetic neural responses during acute cervical non-invasive vagus nerve stimulation (nVNS) and subsequent static handgrip (SHG) exercise with post-exercise...
PURPOSE: This study aimed to investigate cardiovascular and sympathetic neural responses during acute cervical non-invasive vagus nerve stimulation (nVNS) and subsequent static handgrip (SHG) exercise with post-exercise circulatory occlusion (PECO) in healthy humans. METHODS: Ten healthy adults (5 men and 5 women, 33 ± 9 [standard deviation] yrs) participated in this double-blinded, randomized, crossover study. Each participant was studied twice on two separate days, with approximately 4 weeks apart: once during the actual cervical nVNS and once during sham stimulation for 4 min each. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured during nVNS and sham stimulation. In addition, participants performed SHG at 40 % of maximal voluntary contraction until fatigue, followed by 2-min PECO to isolate muscle metaboreflex activation before and after each stimulation. RESULTS: During both nVNS and sham stimulation, HR decreased (△-4 ± 4 and △-4 ± 5 bpm; both P < 0.001), and MSNA increased (△4 ± 6 and △2 ± 3 bursts/min; both P < 0.001) in all participants, although MAP remained unchanged (P = 0.312). However, these responses did not differ between nVNS and sham stimulation (all P > 0.05). Additionally, there were no differences in cardiovascular and MSNA responses to fatiguing SHG and PECO between stimulations (all P > 0.05). CONCLUSION: Compared to the sham condition, cervical nVNS had no significant impact on cardiovascular variables and MSNA during acute stimulation, nor on the responses to SHG or PECO. These findings suggest that cervical nVNS has no or minimal acute effect on sympathetic neural (re)activity in healthy adults.
Colonic mucosal TRPA1 expression profiles in irritable bowel syndrome and its correlation to symptom severity: An exploratory study.
Groen SR, Keszthelyi D, Wilms E … +8 more , Huig J, Xu P, Elizalde M, Vork L, Jonkers DMAE, Helyes Z, Masclee AAM, Weerts ZZRM
Auton Neurosci · 2025 Jun · PMID 40157122 · Publisher ↗
INTRODUCTION: Visceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS). A putative involvement of the Transient Receptor Potential Ankyrin-1 (TRPA1) cation channel has been suggested by several animal st...
INTRODUCTION: Visceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS). A putative involvement of the Transient Receptor Potential Ankyrin-1 (TRPA1) cation channel has been suggested by several animal studies. Main objective of this study is to assess location-specific TRPA1 expression in the colonic mucosa and its correlation with symptom severity in IBS patients. METHODS: Biopsies were obtained from the sigmoid of 30 IBS patients (Rome III; median age 39.0 years, 80 % female) and 23 healthy controls (median age 22.7 years, 43.5 % female). Additional biopsies of the proximal colon were obtained in 24 IBS patients. TRPA1 expression levels were measured in duplicate by quantitative reverse-transcriptase-polymerase-chain-reaction, normalized to GAPDH, and assessed as relative mRNA values using the -2 method. In IBS patients, symptoms were assessed and correlated with TRPA1 expression. RESULTS: Relative TRPA1 expression in the sigmoid was significantly higher in IBS patients compared to healthy controls (P < 0.001). Within IBS patients TRPA1 expression of sigmoid biopsies was significantly higher compared to proximal colon samples (p < 0.001). No significant correlation was found between TRPA1 expression in sigmoid or proximal colon samples and the symptom severity (abdominal discomfort, abdominal pain and bloating). CONCLUSION: These findings suggest a potential role for the TRPA1 related pathway as a target for IBS treatment in the future. Since there was no correlation found in the current exploratory study between TRPA1 expression and symptom severity, further research towards the clinical relevance of the increased TRPA1 expression in IBS-patients along with its location-specific expression is warranted.
Dissecting the exercise pressor reflex in heart failure: A multi-step failure.
Iannetta D, Laginestra FG, Wray DW … +1 more , Amann M
Auton Neurosci · 2025 Jun · PMID 40117701 · Full text
The contribution of neural feedback originating from exercising limb muscles to the cardiovascular response to exercise was first recognized nearly 100 years ago. Today, it is well established that this influence is init...
The contribution of neural feedback originating from exercising limb muscles to the cardiovascular response to exercise was first recognized nearly 100 years ago. Today, it is well established that this influence is initiated by the activation of group III and IV sensory neurons with terminal endings located within contracting skeletal muscle. During exercise, these sensory neurons project feedback related to intramuscular mechanical and metabolic perturbations to medullary neural circuits which reflexively evoke decreases in parasympathetic and increases in sympathetic nervous system activity with the purpose of optimizing central and peripheral hemodynamics. Considerable evidence from animal and human studies suggests that the function of this regulatory control system, known as the exercise pressor reflex (EPR), is abnormal in heart failure and exaggerates sympatho-excitation which impairs the hemodynamic response to exercise and contributes to the functional limitations characterizing these patients. This review briefly introduces the key determinants of EPR control in health and covers the impact of heart failure on the integrity of each of its components and overall function. These include the sensitivity of group III/IV muscle afferents, afferent signal transmission in the spinal cord, and the central integration and processing of sensory feedback within the brainstem. Importantly, although most data relevant for this review come from studies in HFrEF, the limited HFpEF-specific insights are included when available. While arguably not part of the EPR, we also discuss the impact of heart failure on the exercise-induced increase of intramuscular stimuli of group III/IV muscle afferents and end-organ responsiveness to sympathetic/neurochemical stimulation.
Renal nerve afferents drive preferential renal sympathoexcitation in response to acute renal ischemia/reperfusion in rats.
Marreiros AC, Milanez MIO, Carvalhal RS … +7 more , Nishi EE, Santos DD, Gil CD, Lantyer R, Knuepfer MM, Bergamaschi CT, Campos RR
Auton Neurosci · 2025 Jun · PMID 40112747 · Publisher ↗
Renal nerve activity is composed of afferent (sensory) and efferent (sympathetic) nerve activity. Ischemia/reperfusion (IR) of the kidney increases renal sympathetic nerve activity (rSNA) and depresses renal function. As...
Renal nerve activity is composed of afferent (sensory) and efferent (sympathetic) nerve activity. Ischemia/reperfusion (IR) of the kidney increases renal sympathetic nerve activity (rSNA) and depresses renal function. As the role of renal afferent fibers in acute renal IR is unclear, we tested the hypothesis that renal IR increases rSNA triggered by renal afferent nerves responding to acute ischemia. Two experimental series were performed in adult male Wistar rats. IR was induced by total obstruction of blood flow to the left kidney by clamping the renal artery for 60 min and reperfusion for 120 min. We recorded MAP, HR, rSNA, and splanchnic sympathetic vasomotor activity (sSNA) in 8 normal IR rats and 6 left kidney deafferented IR rats (IR ARD). Renal deafferentation was performed using capsaicin administration to the left renal nerve 2 weeks before the experiments. Blood samples were collected before ischemia and at the end of reperfusion for total and differential leukocyte counts. Renal ischemia significantly increased rSNA 23 % (20 min: 0,07 ± 0,04mVs P < 0.05) but not sSNA. The increase in rSNA was triggered by activation of renal afferent fibers, since IR significantly reduced rSNA in the IR ARD group maximal decrease in frequency 22 % (180 min: -62 ± 29Δspikes/s) and in amplitude 41 % (-0,29 ± 0, 12mVs, P < 0.05) and induced hypotension and bradycardia. However, no significant difference was observed between groups in blood leukocyte profile, but a significant reduction in renal IL-6 was found in IR ARD, suggesting a reduction in renal inflammation in deafferented IR rats. The results show that renal afferent nerves trigger a preferential increase in rSNA and inflammation in the kidney during acute IR.
Interoception in Parkinson's disease: A narrative review and framework for translational research.
Longardner K, Mabry SA, Chen G … +3 more , Freeman R, Khalsa SS, Beach P
Auton Neurosci · 2025 Jun · PMID 40101537 · Publisher ↗
Parkinson's disease (PD) is the second most common, and the fastest growing, neurodegenerative disease worldwide. Non-motor manifestations, particularly autonomic nervous system dysfunction, are common throughout the dis...
Parkinson's disease (PD) is the second most common, and the fastest growing, neurodegenerative disease worldwide. Non-motor manifestations, particularly autonomic nervous system dysfunction, are common throughout the disease course, in some cases preceding motor symptom onset by years, and are often more disabling and harder to treat than motor symptoms and contribute significantly to disability. An understudied consequence of autonomic and visceral dysfunction in PD is interoception, the neural processing of internal organ system signals. Interoceptive processes form a foundational body-brain interface, mediating basic homeostatic reflexes and complex physiologic and behavioral adaptive responses to internal perturbations. Emerging evidence exists that interoception is impaired in some individuals with PD, potentially explaining why those who have objective evidence of autonomic dysfunction do not always report typical symptoms. Failure to recognize these impairments may lead to missed opportunities for early intervention, particularly in addressing 'silent' autonomic disturbances (e.g., orthostatic hypotension leading to sudden falls, dysphagia leading to aspiration pneumonia). In this narrative review, we synthesize current findings on the neuroanatomical networks underlying interoception, examine clinical manifestations of interoceptive dysfunction across multiple organ systems in PD, and identify key gaps in knowledge. We propose a translational research framework to enhance early detection, symptom management, and intervention strategies for PD. This framework integrates cognitive, mood, and autonomic dysfunctions with clinical factors (disease stage, duration, motor subtype, levodopa status) to understand interoceptive dysfunction within a translational model. This approach highlights novel opportunities for personalized care and improved therapeutic interventions in PD.
Exercise-mediated modulation of autonomic nervous system and inflammatory response in sleep-deprived individuals: A narrative reviews of implications for cardiovascular health.
Saputro RE, Chou CC, Lin YY … +2 more , Tarumi T, Liao YH
Auton Neurosci · 2025 Jun · PMID 40073691 · Publisher ↗
Sleep deprivation is a growing concern in cardiovascular risk, causing physiological disruptions like autonomic dysregulation and inflammation. Recent research indicates that sleep deprivation increases sympathetic nervo...
Sleep deprivation is a growing concern in cardiovascular risk, causing physiological disruptions like autonomic dysregulation and inflammation. Recent research indicates that sleep deprivation increases sympathetic nervous activity while decreasing parasympathetic activity, leading to increased blood pressure, impaired endothelial function, and heightened inflammation. Exercise has emerged as a non-pharmacological approach to increase cardiovascular health. However, the impact of exercise on sleep deprivation-induced changes in autonomic activity and inflammation remains unclear. To explore this, we reviewed studies investigating the effects of acute exercise on autonomic regulation and inflammatory markers following sleep deprivation. We conducted a narrative review of the literature. PubMed/MEDLINE, Google Scholar, and Web of Science (WOS) searched the articles between May 2022 and April 2023. The papers had to: [1] focus on recent studies between 2000 and 2023; [2] consist of sleep deprivation participants; [3] be published in English. Acute moderate- to high-intensity exercise after sleep deprivation may reduce parasympathetic activity, trigger pro-inflammatory cytokines, and delay recovery to normal levels. In contrast, regular exercise routines may mitigate the adverse effects of sleep deprivation on autonomic regulation and reduce systemic inflammation. Sleep deprivation can lead to autonomic imbalance, increased blood pressure, and increased inflammatory responses, which are further amplified by acute exercise, increasing the cardiovascular burden. When sleep deprivation occurs, exercise intensity and timing should be carefully chosen to avoid adverse cardiovascular health risks.
Sympathetic reactivity to emotional stress in women with major depressive disorder.
Autler AS, Darling AM, Skow RJ … +4 more , Young BE, Fadel PJ, Saunders EFH, Greaney JL
Auton Neurosci · 2025 Jun · PMID 40058187 · Full text
Young women, who suffer from major depressive disorder (MDD) at twice the rate as young men, are particularly vulnerable to cardiovascular events triggered by emotional stress, an association that may be partially explai...
Young women, who suffer from major depressive disorder (MDD) at twice the rate as young men, are particularly vulnerable to cardiovascular events triggered by emotional stress, an association that may be partially explained by excessive sympathetic activation. However, no studies have directly measured sympathetic activity during acute emotional stress in young women with MDD. We hypothesized that the muscle sympathetic nerve activity (MSNA) response to acute emotional stress would be greater in young women with MDD (18-30 yrs) compared to healthy non-depressed young women. MSNA (peroneal microneurography) and beat-to-beat blood pressure (BP; finger photoplethysmography) were measured at rest and during acute emotional stress evoked by viewing negative images selected from the International Affective Picture System in 17 healthy young women and in 30 young women with MDD of mild-to-moderate severity (unmedicated). There were no group differences in either the peak increase in MSNA (Δ0.1 ± 2.9 healthy vs. Δ2.0 ± 4.9 bursts/min MDD; p = 0.45) or the peak increase in mean arterial pressure (Δ0.6 ± 3.5 healthy vs. Δ1.4 ± 2.1 mmHg MDD; p = 0.67) in response to viewing negative images. However, in young women with MDD, MSNA reactivity to viewing negative images was positively related to current depressive symptom severity (r = 0.49; p = 0.04). Although these data indicate only minor MSNA responses to viewing negative images, they also highlight that sympathetic-cardiovascular reactivity to an acute, passive emotional stress stimulus is not exaggerated in young women with MDD. However, more severe current depressive symptoms may amplify emotional stress-induced sympathetic activation, thereby increasing cardiovascular risk.
The effects of isometric handgrip and post-exercise circulatory occlusion on muscle sympathetic nerve activity: A systematic review and meta-analysis.
Maier LE, Meyer SE, Deprato A … +4 more , Busch S, Sivak A, Davenport MH, Steinback CD
Auton Neurosci · 2025 Jun · PMID 40058186 · Publisher ↗
This systematic review and meta-analysis was conducted to identify a 'normative' sympathetic response to isometric handgrip and post-exercise circulatory occlusion. Structured searches of databases were performed until J...
This systematic review and meta-analysis was conducted to identify a 'normative' sympathetic response to isometric handgrip and post-exercise circulatory occlusion. Structured searches of databases were performed until June 2024. We included all primary studies (other than systematic reviews and meta-analyses), and inclusion criteria were: population (all populations); intervention (isometric handgrip and post-exercise circulatory occlusion); comparator (baseline); and outcome (MSNA). One-hundred fifty-eight studies (n = 3551) were included. Burst frequency was elevated during handgrip (n = 1853; MD, 12.19bursts/min; 95 % CI, 11.09, 13.28; I = 94 %; p < 0.00001) and during PECO (n = 948; MD, 11.42bursts/min; 95 % CI, 10.10, 12.75; I = 65 %; p < 0.00001). A similar pattern was observed for burst incidence in handgrip (n = 1074; MD, 8.50bursts/100 hbs; 95 % CI, 7.07, 9.93; I2 = 39 %; p < 0.00001) and PECO (n = 560; MD, 14.87bursts/100 hbs; 95 % CI, 12.65, 17.10; I2 = 43 %; p < 0.00001). Subgroup analyses indicated a larger response in burst frequency and incidence during handgrip exercise in healthy individuals compared to individuals with cardiovascular diseases or other conditions (p < 0.05). A similar response in burst frequency to PECO was observed with subgroup differences between healthy individuals and individuals with cardiovascular diseases and other conditions (p < 0.00001). MSNA is elevated during handgrip exercise across a range of handgrip protocols, populations, and co-interventions. Increases in MSNA during PECO supports the role of the metaboreflex separate to the exercise pressor reflex. A blunted sympathetic response to handgrip and PECO in individuals with cardiovascular diseases contradicts the current understanding of general sympathetic hyperactivity in these populations.
Changes and prognostic significance of autonomic cardiac regulation during ageing.
Karhumaa E, Vuoti A, Kiviniemi AM … +5 more , Junttila MJ, Tulppo MP, Huikuri HV, Ukkola OH, Perkiömäki JS
Auton Neurosci · 2025 Apr · PMID 40023882 · Publisher ↗
BACKGROUND: Data on the changes of heart rate variability (HRV) and their prognostic significance during ageing are limited. METHODS: HRV analyzes were done from standardized 45-min ECG recordings, which consisted of 15 ...
BACKGROUND: Data on the changes of heart rate variability (HRV) and their prognostic significance during ageing are limited. METHODS: HRV analyzes were done from standardized 45-min ECG recordings, which consisted of 15 min recordings in lying down, sitting positions and during walking. We used time domain-, frequency domain- and non-linear methods to estimate HRV. The baseline ECG recordings were done in 1991-1993 (n = 783) and follow up recordings were done in 2013-2014 (n = 466). Endpoints were reviewed in 2021. RESULTS: During a mean follow-up of 22.1 ± 0.7 years, high-, low- and very-low-frequency powers (HF, LF, VLF), standard deviation of RR intervals (SDNN), the short-term fractal-like scaling exponent analyzed by the detrended fluctuation analysis (DFA1) and approximate entropy (ApEn) decreased statistically significantly (p-values from <0.05 to <0.001). Larger decrease of VLF(ln) and LF(ln) predicted total and cardiovascular (CV) mortality in the multivariate model (p-values from <0.05 to <0.001). Baseline natural logarithm of LF (LF(ln)) dichotomized and DFA1 had the strongest prognostic value on total and CV-mortality in multivariate analysis after adjustments with relevant clinical characteristics. Also, lower values of baseline ApEn retained their predictive power for total mortality and decreased ratio of LF to HF (LF/HF) for CV-mortality after adjustments. CONCLUSIONS: Almost all the HRV parameters decreased during ageing. Larger decrease of VLF(ln) and LF(ln) predicted total and CV-mortality after adjustments indicating that larger attenuation in cardiac autonomic regulation during ageing yields prognostic information. Of the baseline HRV parameters LF(ln) dichotomized and DFA1 had the strongest prognostic value on total and CV-mortality.
Quantitative serum proteomic analysis for biomarker discovery in post-COVID-19 postural orthostatic tachycardia syndrome (PC-POTS) patients.
Ryu T, Adler BL, Jeong SJ … +4 more , Lee DC, Hoke A, Na CH, Chung T
Auton Neurosci · 2025 Apr · PMID 40022872 · Publisher ↗
Postural orthostatic tachycardia syndrome (POTS) is a chronic, debilitating condition that is characterized by an excessive increase in heart rate upon orthostatic challenge. Before the COVID-19 pandemic, POTS affected 0...
Postural orthostatic tachycardia syndrome (POTS) is a chronic, debilitating condition that is characterized by an excessive increase in heart rate upon orthostatic challenge. Before the COVID-19 pandemic, POTS affected 0.5 % to 1 % of the U.S. population. Since the pandemic, the incidence has risen sharply, adding an estimated 6-7 million new cases in the U.S. Despite its importance, there is currently no reliable biomarker for POTS, leading to significant diagnostic delays. A major hurdle in identifying biomarkers is the heterogeneous nature of the syndrome. To address this, we focused on a homogeneous subgroup of post-COVID-19 POTS (PC-POTS) patients. We conducted quantitative proteomics on sera from 9 PC-POTS patients and 9 healthy controls, identifying 31 proteins with significantly different abundances in PC-POTS patients. Most elevated proteins were linked to actin filaments or immune functions/inflammation. Weighted Gene Co-Expression Network Analysis revealed module 7 (M7) correlated strongly with PC-POTS diagnosis and related traits. The key proteins in M7 included MTPN, TAGLN2, ADP-ribosylation factor 1, PDLIM1, PPIA, CNN2, LGALSL, TXN, TLN1, TUBA4A, IL4, TREML1, GP1BA, and, all highly correlated with these traits. Cell-type enrichment analysis revealed that M7 was highly associated with immune and neuronal cells. The main pathways identified in M7 included the integrin signaling pathway, blood coagulation, and glycolysis. These findings suggest that the key proteins in M7 could serve as biomarkers for PC-POTS. This study uses quantitative proteomics to identify potential biomarkers that differentiate PC-POTS patients from healthy controls, establishing a foundation for further research and validation.
Cardiac Vagal Nerve Activity During Exercise: New insights and future directions.
Shanks J, Ramchandra R
Auton Neurosci · 2025 Apr · PMID 40010037 · Publisher ↗
A new paradigm is emerging in which cardiac vagal nerve activity is maintained and increases during exercise. This paradigm challenges decades of studies that have quoted a withdrawal of cardiac vagal activity during exe...
A new paradigm is emerging in which cardiac vagal nerve activity is maintained and increases during exercise. This paradigm challenges decades of studies that have quoted a withdrawal of cardiac vagal activity during exercise. Here, we outline the existing evidence for increased cardiac vagal activity. We also explain why previous indirect methods used to measure vagal activity might have indirectly led to incorrect conclusions about the role of the cardiac vagus during exercise. We will review evidence that vagal control of the sinoatrial node and the ventricles differs and how vagal neurotransmitters other than acetylcholine may regulate cardiac function during exercise. We will also suggest future directions for research to uncover how the cardiac vagus influences cardiac function and the mechanisms behind the increase in cardiac vagal nerve activity during exercise.
Hypertonic saline solution evokes cardiovascular recovery in hemorrhagic rats dependent on GABA A and β-adrenergic transmission in the subfornical organ.
da Silva ABC, Marques SM, Fajemiroye JO … +5 more , Colombari E, Xavier CH, Ferreira-Neto ML, Naves LM, Pedrino GR
Auton Neurosci · 2025 Apr · PMID 39983353 · Publisher ↗
BACKGROUND: Studies have reported the use of a hypertonic saline solution (HSS) for the treatment of hypotensive hemorrhage (HH). Despite the established role of central mechanisms in the cardiovascular recovery induced...
BACKGROUND: Studies have reported the use of a hypertonic saline solution (HSS) for the treatment of hypotensive hemorrhage (HH). Despite the established role of central mechanisms in the cardiovascular recovery induced by HSS during HH, the involvement of the Subfornical Organ (SFO) in these responses remains to be elucidated. The present study evaluated the role of SFO and adrenergic neurotransmission in the nucleus in the cardiovascular responses to HSS infusion in hemorrhagic rats. METHODS: Mean arterial pressure (MAP), heart rate (HR), and aortic vascular resistance (AVR) were recorded in Wistar rats. HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. Nanoinjections of saline (NaCl; 0.15 M; control group; n = 7), muscimol (4 mM; GABAergic agonist; muscimol group; n = 7), or propranolol (10 mM; non-selective β-adrenergic blocker; propranolol group; n = 7) in SFO were performed 10 min after the onset of blood withdrawal, followed by HSS infusion (NaCl; 3 M; 1.8 ml∙kg) 20 min after the beginning of HH. RESULTS: Hypotension, bradycardia, and aortic vasoconstriction were observed in all groups During HH. Sodium overload reestablished MAP and HR while maintaining aortic vasoconstriction in the control group. Activation of GABA A receptors or β-adrenergic receptor blockade in the SFO prevents HSS-induced recovery of MAP and HR. In addition, maintenance of aortic vasoconstriction induced by HSS infusion was abolished by SFO inhibition. CONCLUSIONS: The results suggest that the integrity of SFO neurons and β-adrenergic neurotransmission are essential for cardiovascular recovery promoted by sodium overload in hemorrhagic rats.
Monotherapy with tolterodine or mirabegron is insufficient for ameliorating cyclophosphamide-induced bladder overactivity in rats.
Fjelltveit H, Carlsson T, Perez F … +3 more , Aydogdu O, Patel B, Winder M
Auton Neurosci · 2025 Apr · PMID 39977963 · Publisher ↗
Monotherapy continues to be the most common pharmacological treatment option for patients with overactive bladder (OAB), despite evidence indicating that it may have inferior efficacy compared to combination therapy. Thi...
Monotherapy continues to be the most common pharmacological treatment option for patients with overactive bladder (OAB), despite evidence indicating that it may have inferior efficacy compared to combination therapy. This seems to be especially true for patients with concomitant cystitis. The current study examined the effects of monotherapy with either the antimuscarinic tolterodine or the β3 agonist mirabegron on bladder overactivity induced by bladder inflammation. Further, the possible involvement of nitric oxide (NO) was studied. For this purpose, rats were pretreated with either drug for 10 days. Bladder inflammation was induced by intraperitoneal injection with cyclophosphamide, with saline serving as control. Micturition parameters were assessed in a metabolic cage. Meanwhile, urine samples were collected and further analysed for NO content. After 16 h, the animals were euthanized, and their bladders were excised and examined immunohistochemically for signs of inflammation. Cyclophosphamide treatment led to bladder overactivity and obvious signs of inflammation. Neither treatment with tolterodine nor mirabegron could significantly alleviate the induced overactivity or the observed inflammation. Further, while induction of inflammation led to a significant increase in NO production, neither drug seemed to act by further enhancing its production. On the contrary, treatment with either tolterodine or mirabegron significantly decreased NO production in cyclophosphamide treated rats. Considering previous findings showing significant improvement by combination therapy, the current study indirectly implies this as the superior treatment option. Further studies are needed to verify the involvement, or lack thereof, of NO in the mechanism of action of drugs used to treat OAB.
Inter-individual variability in muscle sympathetic nerve activity at rest and during exercise: Disconnection with blood pressure.
Teixeira AL, Millar PJ
Auton Neurosci · 2025 Apr · PMID 39970811 · Publisher ↗
Microneurographic recordings of muscle sympathetic nerve activity (MSNA) have provided fundamental insight into sympathetic discharge patterns at rest and during exercise in health and disease. A key feature of MSNA reco...
Microneurographic recordings of muscle sympathetic nerve activity (MSNA) have provided fundamental insight into sympathetic discharge patterns at rest and during exercise in health and disease. A key feature of MSNA recordings at rest is a large inter-individual variability, even among healthy adults. The physiological consequences of inter-individual variability in MSNA are commonly discussed as being associated with the regulation of resting blood pressure. However, available evidence from large cross-sectional analyses demonstrate a near absence of an association between resting MSNA and blood pressure. Less appreciated, MSNA also exhibits inter-individual variability in response to stress, such as exercise. Again, the consequences of variability in MSNA are unclear and can be dissociated from the blood pressure response, particularly at low-to-moderate intensity muscle contractions for short durations (≤2 min). In this brief review, we summarize several examples of how inter-individual variability in MSNA is unrelated to blood pressure control at rest and during exercise and discuss potential mechanisms responsible for this observation, and key methodological considerations for future study design and interpretation. Additionally, we highlight several unanswered questions that could pave the way for future investigations in the field.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe