Baseline Muscle Sympathetic Nerve Activity Research Articles

Sympathoinhibition during cardiopulmonary baroreceptor loading is attenuated in older females.

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 years) and eleven younger females (20±1 years) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0º), and their lower limbs were passively lifted at 10º, 20º, 30º, and 40º (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 compared to 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 40º 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 40º 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.

Sex Differences in Hemodynamic and Autonomic Reactivity during Cold Pressor Test in Chronic Kidney Disease

Introduction: Chronic kidney disease (CKD) is characterized by sympathetic nervous system (SNS) overactivity that contributes to increased cardiovascular risk. Hemodynamic reactivity during the cold pressor test (CPT) has been widely used to evaluate sympathetic neural control in patient populations, and increased neurocardiovascular reactivity to CPT has been shown to predict greater risk of future cardiovascular events. Prior studies have suggested that males with CKD have higher long-term cardiovascular disease risk compared to females with CKD; however, whether sex differences in neurocardiovascular responsivity during CPT exists within CKD remains unknown. Objectives: Our primary objective was to evaluate potential sex differences in hemodynamic and autonomic reactivity during CPT in patients with CKD. Hypothesis: Males with CKD have an augmented pressor and sympathetic response to sympathoexcitation induced by CPT compared with females with CKD. Methods: Patients with CKD (Stage III and IV) with stable renal function were included. Continuous beat to beat blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) by microneurography were measured at rest for 10 minutes and during CPT that consisted of immersion of the hand to the wrist in ice water (4–5 °C) for one minute, followed by a 5-min recovery period. Results: 25 participants with CKD were included (N= 14 male, N=11 female). There were no differences in baseline characteristics, resting hemodynamics or MSNA between male and female groups. Males with CKD had a steeper rate of increase and higher peak levels of diastolic BP (DBP, 101±3 vs 87±3; p=0.008) and mean arterial BP (MAP, 130±4 vs 112±5 mm Hg, p=0.023) during CPT compared to females with CKD, respectively. Conversely, females with CKD had a steeper rate of increase in HR during CPT compared to males. MSNA increased in both males and females during CPT; however, there was no difference in MSNA reactivity during CPT between groups. Conclusions: Males with CKD had greater BP reactivity during CPT compared to females with CKD, while females with CKD had greater HR reactivity during CPT compared to males. There was no difference in sympathetic reactivity between groups. Augmented BP reactivity during CPT in males with CKD may contribute to sex differences in cardiovascular disease risk in patients with CKD. Supported by NIH Grants R33AT010457 and R01HL135183. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Sex on Sympatho-inhibitors and Non-inhibitor Phenotypes during Acute Hyperoxia

Acute hyperoxia (i.e., breathing air consisting of 100% oxygen, O2) reduces muscle sympathetic nerve activity (MSNA), positioning hyperoxia as a potential anti-hypertensive therapeutic. However, the link between hyperoxia and MSNA has not been established in females. We tested the hypothesis that males would exhibit greater reductions in MSNA during hyperoxia than females. We tested healthy females (n=18, 27±5yr, body mass index [BMI] 23±3kg/m2) and males (n=13, 27±5yr, 25±3kg/m2) of similar age (P=0.99) and BMI (P=0.08). Integrated MSNA, blood pressure, and end-tidal O2 (ETO2) and CO2 (ETCO2) were measured during normal room air breathing (BSL; 3-min) and hyperoxic breathing (100% O2; 3-min). Integrated MSNA was quantified as burst frequency (BF; bursts/min), amplitude (BA; a.u.), and total MSNA (a.u.); blood pressure was quantified as mean arterial pressure (MAP). Baseline MSNA BF was not different between females and males (24±7 vs 23±8 bursts/min, respectively, P=0.68); MAP was lower in females than males (85±7 vs 93±7 mmHg; p<0.01). Hyperoxia increased ETO2 (effect of cond: p<0.01) and reduced ETCO2 (effect of cond: p<0.01) in a manner similar between sexes for ETO2 (sex*cond: P=0.56) whereas ETCO2 decreased more in females than males (sex*cond: P=0.01). Overall, hyperoxia evoked reductions in MSNA BF (effect of cond: P=0.02) but not BA (effect of cond: P=0.80) or total MSNA (effect of cond: P=0.26). Nadir MSNA responses during hyperoxia unveiled sex differences insofar as total MSNA was reduced consistently only in males (sex*cond: P=0.04); within the females we observed the presence of sympatho-inhibitors and non-inhibitors. Whereas female and male inhibitors reduced total MSNA via substantial reductions in BF and non-significant reductions in BA, female non-inhibitors demonstrated limited reductions in BF (P=0.11 vs inhibitors) coupled with increases in BA (p<0.01 vs inhibitors), resulting in no net change in total MSNA (p<0.01 vs inhibitors). Overall, these findings indicate sex differences exist in the sympathetic response to hyperoxia, in marked variability in the female sympathetic response to acute hyperoxia. The Women and Children's Health Research Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Influence of sex on sympathetic vasomotor outflow responses to passive leg raising in young individuals.

The purpose of this study was to clarify sex differences in the inhibition of sympathetic vasomotor outflow which is caused by the loading of cardiopulmonary baroreceptors. Ten young males and ten age-matched females participated. The participants underwent a passive leg raising (PLR) test wherein they were positioned supine (baseline, 0º), and their lower limbs were lifted passively at 10º, 20º, 30º, and 40º. Each angle lasted for 3min. Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. Baseline MSNA was lower in females compared to males. MSNA burst frequency was decreased during the PLR in both males (- 6.2 ± 0.4 bursts/min at 40º) and females (- 6.5 ± 0.4 bursts/min at 40º), but no significant difference was detected between the two groups (P = 0.61). These results suggest that sex has minimal influence on the inhibition of sympathetic vasomotor outflow during the loading of cardiopulmonary baroreceptors in young individuals.

Greater resting muscle sympathetic nerve activity reduces cold pressor autonomic reactivity in older women, but not older men.

Previous work demonstrates augmented muscle sympathetic nerve activity (MSNA) responses to the cold pressor test (CPT) in older women. Given its interindividual variability, however, the influence of baseline MSNA on CPT reactivity in older adults remains unknown. Sixty volunteers (60-83y; 30 women) completed testing where MSNA (microneurography), blood pressure (BP), and heart rate (HR) were recorded during baseline and a 2-min CPT (~4°C). Participant data were terciled by baseline MSNA (n=10/group); comparisons were made between the high baseline men (HM) and women (HW), and low baseline men (LM) and women (LW). By design, HM and HW, vs. LM and LW, had greater baseline MSNA burst frequency (37±5 and 38±3 vs. 9±4 and 15±5 bursts/min) and burst incidence (59±14 and 60±8 vs. 16±10 and 23±7 bursts/100hbs; both P<0.001). However, baseline BP and HR were not different between the groups (all P>0.05). During the CPT, there were no differences in the increase in BP and HR (all P>0.05). Conversely, ΔMSNA burst frequency was lower in HW vs. LW (8±9 vs. 22±12 bursts/min; P=0.012) yet was similar in HM vs. LM (17±12 vs. 19±10 bursts/min, P=0.994). Further, ΔMSNA burst incidence was lower in HW vs. LW (9±13 vs. 28±16 bursts/100hbs; P=0.020), with no differences between HM vs. LM (21±17 vs. 31±17 bursts/100hbs; P=0.455). Our findings suggest that heightened baseline activity in older women attenuates the typical CPT-mediated increase in MSNA without changing cardiovascular reactivity. While the underlying mechanisms remain unknown, altered sympathetic recruitment or neurovascular transduction may contribute to these disparate responses.

Effect of adaptive servo-ventilation for central sleep apnoea in systolic heart failure on muscle sympathetic nerve activity: a SERVE-HF randomised ancillary study.

Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA. HFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea-hypopnoea index (AHI) ≥15 events·h-1 with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed. 40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h-1). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min-1 at baseline to 44.6±11.2 bursts·min-1; ASV group: 43.0±9.0 bursts·min-1 at baseline to 42.74±9.45 bursts·min-1). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective. Suppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.

The relationship between muscle sympathetic nerve activity and systemic hemodynamics is altered in women with uterine fibroids.

Women with uterine fibroids (UF), benign tumors of the myometrium, have a higher prevalence of hypertension than women without UF. The cause for this relationship is unclear. Muscle sympathetic nerve activity (MSNA) is a regulator of arterial blood pressure, and it is possible that variations in MSNA predispose women with UF to develop hypertension. The purpose of this study was to assess baseline blood pressure and MSNA and the relationships between MSNA and systemic hemodynamics in women with and without UF. We measured blood pressure (brachial intra‐arterial line), MSNA (microneurography), and systemic hemodynamics (total peripheral resistance and cardiac output) at rest in 14 healthy, normotensive, premenopausal women with UF (42 ± 2 years old) and 9 healthy, normotensive, premenopausal women without UF (41 ± 2 years old). Baseline blood pressure and MSNA did not differ between groups (p > 0.05 for both). In women with UF, there was a positive correlation between MSNA and total peripheral resistance (r = 0.75, p = 0.02), as well as a negative correlation between MSNA and cardiac output (r = −0.73, p = 0.03). In contrast, these relationships were not seen in women without UF (p > 0.05 for both relationships). These data suggest that autonomic interactions with systemic hemodynamics, and thus blood pressure regulation, are different in healthy women with UF compared to healthy women without UF.

Sympathetic Responses to Isometric Handgrip Exercise in Women following Preeclamptic Pregnancies

Women who have had preeclamptic (PE) pregnancies are at increased risk for developing cardiovascular diseases later in life. One potential mechanism that may mediate this increased risk is sympathetic dysregulation. Indeed, there is evidence for elevated muscle sympathetic nerve activity (MSNA) both during and following PE pregnancies. Moreover, previously PE (PPE) women may demonstrate impaired MSNA responses during stress, although this has only been examined to a limited extent. Therefore, we tested the hypothesis that MSNA responses to isometric hand grip exercise (HG) would be greater in PPE women (n=6, age 31±6 years, BMI 29±5 kg/m2, 17±4 months postpartum) compared with women who had a healthy pregnancy (HP; n=8, age 29±2, BMI 25±4 kg/m2, 14±4 months postpartum). MSNA (peroneal nerve microneurography), mean arterial pressure (MAP; finger photoplethysmography), and total peripheral resistance (TPR; MAP/cardiac output), were assessed at baseline, during a 2‐min HG protocol, and during 2‐min post‐exercise circulatory occlusion (PECO). As previously reported, baseline MSNA was higher in PPE than HP (22±7 vs 13±5 bursts/min, P=0.01). Baseline MAP was not different between PPE and HP (94±11 vs 89±9 mmHg, P=0.23), nor was TPR (13±3 vs 13±2 mmHg/L/min, P=0.63). During HG, MSNA was greater in PPE than HP (24±8 vs 16±6 bursts/min, P=0.03), whereas MAP was not different between PPE and HP (95±12 vs 95±11 mmHg, P=0.99), nor was TPR (13±3 vs 14±2 mmHg/L/min, P=0.39). During PECO, no differences were observed between PPE and HP women in MSNA (26±8 vs 18±6 bursts/min, P=0.08), MAP (93±12 vs 96±12 mmHg, P=0.70), or TPR (12±3 vs 15±2 mmHg/L/min, P=0.18). These findings indicate that PPE women demonstrate exaggerated MSNA during isometric HG exercise relative to HP women, although the role of the metaboreflex in mediating this effect, as assessed using PECO, remains unclear. Importantly, these data also demonstrate that young PPE women were able to buffer the deleterious cardiovascular outcomes of elevated MSNA such that MAP and TPR outcomes were similar to age‐matched HP women during all conditions.

Sex differences in sympathetic neurovascular and neurohemodynamic relationships during cold pressor test.

Muscle sympathetic nerve activity (MSNA) affects vascular resistance differently in women and men. However, whether this sex difference persists during pronounced increases in MSNA remains unclear. Therefore, the purpose of this study was to examine sex differences in neurovascular transduction during cold pressor test (CPT)-mediated sympathoexcitation. Integrated peroneal MSNA (microneurography) was measured at rest and during a 3-min CPT in young healthy women (n = 11) and men (n = 10). Mean arterial pressure (MAP) was measured beat-by-beat (Finometer), and superficial femoral artery blood flow was measured using duplex ultrasound. Femoral vascular resistance (FVR) was quantified as MAP/femoral blood flow (mmHg/mL/min). Baseline MSNA was similar between women and men (14 ± 9 vs. 15 ± 9 bursts/100 heartbeat, respectively; P = 0.83), whereas MAP was lower (86 ± 7 vs. 92 ± 4 mmHg; P = 0.047), and FVR was greater in women than men (0.54 ± 0.16 vs. 0.36 ± 0.15 mmHg/mL/min; P = 0.02). CPT-induced increases in MSNA were similar between the sexes (19 ± 11 vs. 26 ± 14 bursts/100 heartbeat; P = 0.26) whereas increases in MAP (7 ± 3 vs. 10 ± 3 mmHg; P = 0.03) and FVR (3.2 ± 18.6 vs. 26.8 ± 12.8%; P < 0.01) were smaller in women than in men. Within men, CPT- induced increases in MSNA predicted increases in MAP (R2 = 0.51, P = 0.02) and FVR (R2 = 0.49, P = 0.02). However, MSNA did not predict MAP (R2 = 0.11, P = 0.35) or FVR (R2 = 0.07, P = 0.46) in women. Our findings demonstrate that men experience robust CPT-induced MAP responses that are driven by both neurovascular (MSNA-FVR) and neurohemodynamic (MSNA-MAP) coupling. These relationships were not observed in women, indicating that even during pronounced increases in sympathetic outflow, MSNA is not predictive of vascular nor blood pressure outcomes in young healthy women.

Impact of Resting Differences in Muscle Sympathetic Nerve Activity on Hemodynamic and Neural Responses to Exercise

Resting muscle sympathetic nerve activity (MSNA) displays high inter‐individual variability, yet the neural characteristics of those with high vs. low MSNA and resultant cardiovascular consequences are largely unclear. The purpose of this study was to examine blood pressure (BP) variability at rest and during exercise in individuals with high vs. low resting MSNA, and to characterize differences in resting sympathetic and cardiac baroreflex sensitivity (cBRS), in order to understand the accompanying neural characteristics and cardiovascular consequences of different levels of vasoconstrictor outflow. We retrospectively analyzed MSNA (microneurography) and continuous BP (Finometer) obtained at rest and during 2 minutes of static handgrip exercise at 30% maximal voluntary contraction from 60 young healthy men (n=30) and women (n=30). Within each sex, data was split into tertiles based on resting MSNA burst frequency and a comparative analysis was performed on the highest vs. lowest MSNA groups. BP variability was calculated as the beat‐to‐beat standard deviation. Spontaneous sympathetic baroreflex sensitivity (sBRS) was calculated using a weighted linear regression between diastolic blood pressure (DBP) and MSNA burst incidence. Threshold values (T50) were obtained by calculating the resting DBP associated with 50% of the MSNA bursts. cBRS was determined using the sequence technique. As expected, resting MSNA burst frequency was different between high and low groups (30±4 vs. 14±6 bursts/min [mean±SD], p&lt;0.01), however, baseline anthropometrics, BP, heart rate, and cBRS sensitivity were not different (all, p&gt;0.05). Resting DBP variability was lower in the high group (4±1 vs. 5±2 mmHg, p=0.05). sBRS was higher in the high group (−5.4±1.9 vs. −4.6±1.6 bursts/100 heartbeats/mmHg, p&lt;0.01), and was correlated with resting MSNA (r=−0.46, p&lt;0.01). T50 did not differ between the groups (60 vs. 55 mmHg, p&gt;0.05), however, the prevailing mean DBP was above the T50 DBP to a lower extent in the high group (mean DBP – T50 DBP: 10±3 vs. 18±7 mmHg, p&lt;0.01), and this value was negatively correlated with resting MSNA burst incidence (r=−0.76, p&lt;0.01). During static handgrip exercise, BP and heart rate increased similarly in both groups (all, p&gt;0.05), yet the increase in MSNA burst frequency was smaller in the high group (Δ 4±7 vs 10±6 bursts/min, p&lt;0.01); similar results were obtained using MSNA burst incidence and total MSNA (both p&lt;0.01). The change in burst frequency was unrelated to resting sBRS (r=0.23, p&gt;0.05). Systolic BP variability was lower in the high group during exercise (7±3 vs 10±5 mmHg, p&lt;0.05), but DBP variability was not different. In conclusion, differences in resting MSNA are unrelated to resting and exercising BP, but are likely associated with inter‐individual differences in the degree of BP variability and arterial baroreflex‐mediated suppression of MSNA. Further, baseline MSNA was found to influence the magnitude of the change during static handgrip exercise, though the hemodynamic consequences of these differences, and mechanisms responsible warrant further research.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant; Canada Foundation for InnovationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Exercise Training Increases Metaboreflex Control in Patients with Obstructive Sleep Apnea.

We demonstrated that patients with obstructive sleep apnea (OSA) have reduced muscle metaboreflex control of muscle sympathetic nerve activity (MSNA). In addition, exercise training increased muscle metaboreflex control in heart failure patients. We tested the hypothesis that exercise training would increase muscle metaboreflex control of MSNA in patients with OSA. Forty-one patients with OSA were randomized into the following two groups: 1) nontrained (OSANT, n = 21) and 2) trained (OSAT, n = 20). Muscle sympathetic nerve activity was assessed by microneurography technique, muscle blood flow (FBF) by venous occlusion plethysmography, heart rate by electrocardiography, and blood pressure with an automated oscillometric device. All physiological variables were simultaneously assessed at rest, during isometric handgrip exercise at 30% of the maximal voluntary contraction, and during posthandgrip muscle ischemia (PHMI). Muscle metaboreflex sensitivity was calculated as the difference in MSNA between PHMI and the rest period. Patients in the OSAT group underwent 72 sessions of moderate exercise training, whereas patients in the OSANT group were clinical follow-up for 6 months. The OSANT and OSAT groups were similar in anthropometric, neurovascular, hemodynamic and sleep parameters. Exercise training reduced the baseline MSNA (34 ± 2 bursts per minute vs 25 ± 2 bursts per minute; P < 0.05) and increased the baseline FBF (2.1 ± 0.2 mL·min per 100 g vs 2.4 ± 0.2 mL·min per 100 g; P < 0.05). Exercise training significantly reduced MSNA levels and increased FBF responses during isometric exercise. Exercise training significantly increased MSNA responses during PHMI (Δ6.5 ± 1 vs -1.7 ± 1 bursts per minute, P < 0.01). No significant changes in FBF or hemodynamic parameters in OSANT patients were found. Exercise training increases muscle metaboreflex sensitivity in patients with OSA. This autonomic change associated with increased muscle blood flow may contribute to the increase in exercise performance in this set of patients.

Aging Alters the Relative Contributions of the Sympathetic and Parasympathetic Nervous System to Blood Pressure Control in Women.

Autonomic support of blood pressure increases with age in humans. Large differences exist in the dose of trimethaphan (TMP) required for ganglionic blockade in young and older women. We asked whether differences in the dose of TMP required to achieve ganglionic blockade are because of differences in the relative contributions of the sympathetic and parasympathetic nervous system in control of blood pressure with age. Muscle sympathetic nerve activity (microneurography, peroneal nerve), heart rate (HR), and blood pressure were recorded before and during incremental doses of TMP camsylate until ganglionic blockade was achieved (absence of muscle sympathetic nerve activity and <5-bpm increase in HR during a valsalva maneuver; final TMP dose, 1-7 mg/min). HR variability was analyzed from the ECG waveform (WinCPRS). The dose of TMP required to achieve ganglionic blockade is positively related to basal HR variability, where women with high HR variability require a higher dose of TMP to achieve ganglionic blockade. In contrast, baseline muscle sympathetic nerve activity is inversely related with the dose of TMP required to achieve ganglionic blockade, such that women with high basal muscle sympathetic nerve activity required a lower dose of TMP. As such, the change in HR with ganglionic blockade was positively related, and the change in mean arterial pressure was inversely related, with the dose of TMP required to achieve ganglionic blockade. These data suggest loss of parasympathetic tone and increased sympathetic tone with aging contribute to the increase in blood pressure with age in women and dictate the dose of TMP that is necessary to achieve ganglionic blockade.

Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise-induced increases in muscle sympathetic nerve activity.

The arterial baroreflex's operating point pressure is reset upwards and rightwards from rest in direct relation to the increases in dynamic exercise intensity. The intraneural pathways and signalling mechanisms that lead to upwards and rightwards resetting of the operating point pressure, and hence the increases in central sympathetic outflow during exercise, remain to be identified. We tested the hypothesis that the central production of angiotensin II during dynamic exercise mediates the increases in sympathetic outflow and, therefore, the arterial baroreflex operating point pressure resetting during acute and prolonged dynamic exercise. The results identify that perindopril, a centrally acting angiotensin converting enzyme inhibitor, markedly attenuates the central sympathetic outflow during acute and prolonged dynamic exercise. We tested the hypothesis that the signalling mechanisms associated with the dynamic exercise intensity related increases in muscle sympathetic nerve activity (MSNA) and arterial baroreflex resetting during exercise are located within the central nervous system. Participants performed three randomly ordered trials of 70° upright back-supported dynamic leg cycling after ingestion of placebo and two different lipid soluble angiotensin converting enzyme inhibitors (ACEi): perindopril (high lipid solubility), captopril (low lipid solubility). Repeated measurements of whole venous blood (n=8), MSNA (n=7) and arterial blood pressures (n=14) were obtained at rest and during an acute (SS1) and prolonged (SS2) bout of steady state dynamic exercise. Arterial baroreflex function curves were modelled at rest and during exercise. Peripheral venous superoxide concentrations measured by electron spin resonance spectroscopy were elevated during exercise and were not altered by ACEi at rest (P≥0.4) or during exercise (P≥0.3). Baseline MSNA and mean arterial pressure were unchanged at rest (P≥0.1; P≥0.8, respectively). However, during both SS1 and SS2, the centrally acting ACEi perindopril attenuated MSNA compared to captopril and the placebo (P<0.05). Arterial pressures at the operating point and threshold pressures were decreased with perindopril from baseline to SS1 with no further changes in the operating point pressure during SS2 under all three conditions. These data suggest that centrally acting ACEi is significantly more effective at attenuating the increase in the acute and prolonged exercise-induced increases in MSNA.

Sympathetic Nervous System Reactivity in Women following Preeclamptic Pregnancies

Women who have had preeclamptic pregnancies are at risk for life‐long cardiovascular disease. However, the factors contributing to this risk have yet to be established. Sympathetic nervous system dysregulation has been proposed to contribute to cardiovascular dysfunction during preeclamptic pregnancies. Therefore, we examined muscle sympathetic nerve activity (MSNA) at baseline and during a chemoreflex stimulus in women 6–24 months postpartum following a preeclamptic pregnancy (PE; n=6, age 28±2 y, BMI 27±3 kg/m2, 17±4 months postpartum). We hypothesized that MSNA responses to apnea would be greater in PE relative to control subjects, that is, women 6–24 months following a healthy pregnancy and with no history of disordered pregnancies (HP; n=6, 31±6 y, BMI 29±5 kg/m2, 17±4 months postpartum). Integrated MSNA recordings were obtained at baseline and during a voluntary end‐inspiratory apnea. Baseline mean arterial pressure (MAP; 87±10 vs 95±10 mmHg, P=0.2), total peripheral resistance (TPR; 13±3 vs 14±1 mmHg/L/min, P=0.4), and heart rate (HR; 74±5 vs 74±13, P=0.9) were similar in PE vs HP. Baseline MSNA was higher in PE compared to HP (26±9 vs 14±6 bursts/100 heartbeats, P&lt;0.01). The voluntary apnea was maintained for a similar duration in PE and HP (44±17 and 45±10 sec, P=0.9), without any difference in mean MAP (93±14 and 99±11, P=0.4), TPR (14±4 and 14±2, P=0.6), or HR (74±8 and 81±22, P=0.5) between groups. To discern between mild and moderate phases of chemoreflex stress, the apnea was divided into initial (i.e. first half) and latter (i.e. second half) phases for subsequent analyses. The initial phase of the apnea elicited a large increase in MSNA in the PE women which exceeded that observed in HP (37±13 vs 19±11, P=0.03, respectively). The peak sympathetic response observed in the latter half of the apnea was similar between PE and HP (56±21 vs 49±13 bursts/100hb, P=0.5). Thus, the sympathetic nervous system response to a mild chemoreflex stimulus is exaggerated in women who have had preeclampsia within the past 6–24 months relative to women without a history of preeclampsia. We have demonstrated that a recent history of preeclampsia is associated with chronic sympathetic activation as well as greater sympathetic reactivity. We propose these changes to the sympathetic nervous system contribute to the life‐long risk for cardiovascular disease in formerly preeclamptic women.Support or Funding InformationFunded by the Paul Titus Fellowship, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Relative burst amplitude of muscle sympathetic nerve activity is an indicator of altered sympathetic outflow in chronic anxiety.

Relative burst amplitude of muscle sympathetic nerve activity (MSNA) is an indicator of augmented sympathetic outflow and contributes to greater vasoconstrictor responses. Evidence suggests anxiety-induced augmentation of relative MSNA burst amplitude in patients with panic disorder; thus we hypothesized that acute stress would result in augmented relative MSNA burst amplitude and vasoconstriction in individuals with chronic anxiety. Eighteen participants with chronic anxiety (ANX; 8 men, 10 women, 32 ± 2 yr) and 18 healthy control subjects with low or no anxiety (CON; 8 men, 10 women, 39 ± 3 yr) were studied. Baseline MSNA and 24-h blood pressure were similar between ANX and CON ( P > 0.05); however, nocturnal systolic blood pressure % dipping was blunted among ANX ( P = 0.02). Relative MSNA burst amplitude was significantly greater among ANX compared with CON immediately preceding (anticipation) and during physiological stress [2-min cold pressor test; ANX: 73 ± 5 vs. CON: 59 ± 3% arbitrary units (AU), P = 0.03] and mental stress (4-min mental arithmetic; ANX: 65 ± 3 vs. CON: 54 ± 3% AU, P = 0.02). Increases in MSNA burst frequency, incidence, and total activity in response to stress were not augmented among ANX compared with CON ( P > 0.05), and reduction in brachial artery conductance during cold stress was similar between ANX and CON ( P = 0.92). Relative MSNA burst amplitude during mental stress was strongly correlated with state ( P < 0.01) and trait ( P = 0.01) anxiety (State-Trait Anxiety Inventory), independent of age, sex, and body mass index. Thus in response to acute stress, both mental and physiological, individuals with chronic anxiety demonstrate selective augmentation in relative MSNA burst amplitude, indicating enhanced sympathetic drive in a population with higher risk for cardiovascular disease. NEW & NOTEWORTHY Relative burst amplitude of muscle sympathetic nerve activity in response to acute mental and physiological stress is selectively augmented in individuals with chronic anxiety, which is a prevalent condition that is associated with the development of cardiovascular disease. Augmented sympathetic burst amplitude occurs with chronic anxiety in the absence of common comorbidities. These findings provide important insight into the relation between anxiety, acute stress and sympathetic activation.

Muscle Metaboreflex Control of Sympathetic Activity in Obstructive Sleep Apnea.

Previous studies report abnormal muscle metaboreflex control of muscle sympathetic nerve activity (MSNA) in obesity, hypertension, and heart failure. We hypothesized that obstructive sleep apnea (OSA) is associated with augmented metaboreflex control of MSNA. Thirty-one sedentary individuals with no comorbidities (age = 52 ± 1 yr, body mass index = 28 ± 1 kg·m) without (control, n = 14) and with OSA (n = 17) defined by polysomnography, underwent echocardiography. HR, blood pressure (BP), MSNA (microneurography), and forearm blood flow measured by venous occlusion plethysmography were continuously measured 4 min at baseline, during 3 min of 30% handgrip static exercise, and during 2 min of post-handgrip muscle ischemia (PHMI). Control and OSA groups were similar in age, body mass index, and ejection fraction. Baseline HR, BP, and forearm blood flow increased similarly during handgrip exercise. Blood pressure remained significantly elevated in relation to baseline during PHMI, but HR and forearm blood flow returned toward baseline during PHMI in both groups. Baseline MSNA was significantly higher in the OSA group than in controls (P < 0.05). During peak 30% static handgrip exercise, MSNA increased significantly in both control and OSA groups, but MSNA responses were higher in patients with OSA. During PHMI, MSNA in control subjects remained significantly elevated compared with that at baseline. In contrast, in patients with OSA, MSNA decreased to baseline values. A significant correlation was found between changes in MSNA due to PHMI and apnea-hypopnea index (r = -0.61, P < 0.001), and with minimum O2 saturation (r = 0.70, P < 0.001). These findings suggest an association between OSA and decreased metaboreflex control of MSNA. Muscle vasodilation during handgrip static exercise is preserved in patients with OSA.

Neuroendocrine Dysregulation in Irritable Bowel Syndrome Patients: A Pilot Study.

Background/AimsIrritable bowel syndrome (IBS) is a multifactorial disorder, involving dysregulation of brain-gut axis. Our aim was to evaluate the neuroendocrine activity in IBS.MethodsThirty IBS and 30 healthy volunteers were enrolled. Psychological symptoms were evaluated by questionnaires. Urinary 5-hydroxyindoleacetic acid, plasma serotonin (5-hydroxytryptamine, 5-HT), endothelin, and neuropeptide Y (NPY), and plasma and urinary cortisol levels were evaluated. Fourteen IBS subjects underwent microneurography to obtain multiunit recordings of efferent postganglionic muscle sympathetic nerve activity (MSNA).ResultsPrevalent psychological symptoms in IBS were maladjustment (60%), trait (40%) and state (17%) anxiety, obsessive compulsive-disorders (23%), and depressive symptoms (23%). IBS showed increased NPY (31.9 [43.7] vs 14.8 [18.1] pmol/L, P = 0.006), 5-HT (214.9 [182.6] vs 141.0 [45.5] pg/mL, P = 0.010), and endothelin [1.1 [1.4] vs 2.1 [8.1] pg/mL, P = 0.054], compared to healthy volunteers. Moreover, plasma NPY, endothelin, cortisol and 5-HT, and urinary 5-hydroxyindoleacetic acid were associated with some psychological disorders (P ≤ 0.05). Despite a similar resting MSNA, after cold pressor test, IBS showed a blunted increase in MSNA burst frequency (+4.1 vs +7.8 bursts/min, P = 0.048; +30.1% vs +78.1%, P = 0.023). Baseline MSNA tended to be associated with urinary cortisol (ρ = 0.557, P = 0.059). Moreover, changes in heart rate after mental stress were associated with urinary cortisol (ρ = 0.682, P = 0.021) and changes in MSNA after mental stress were associated with plasma cortisol (ρ = 0.671, P = 0.024).”ConclusionHigher concentrations of endothelin, NPY, and 5-HT were found to be associated with some psychological disorders in IBS patients together with an altered cardiovascular autonomic reactivity to acute stressors compared to healthy volunteers.

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder.

Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known. Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients. Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation. Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients. Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD. Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress: combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD vs. Controls, MSNA (+8.2±1.0vs. +1.2±1.3burstsmin-1 , P<0.001) and heart rate responses (+3.2±1.1vs. -2.3±1.0beatsmin-1 , P=0.003) were significantly augmented during VRCE. Similarly, in PTSD vs. Controls, MSNA (+21.0±2.6vs. +6.7±1.5burstsmin-1 , P<0.001) and diastolic BP responses (+6.3±1.0vs. +3.5±1.0mmHg, P=0.011) were significantly augmented during MA but not during CPT (P=not significant). In the PTSD group, sympathetic BRS (-1.2±0.2vs. -2.0±0.3burst incidencemmHg-1 , P=0.026) and cardiovagal BRS (9.5±1.4vs. 23.6±4.3msmmHg-1 , P=0.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive-C-reactive protein levels compared to Controls (2.1±0.4vs. 1.0±0.3mgL-1 , P=0.047). Augmented SNS and haemodynamic responses to mental stress, bluntedBRS and inflammation may contribute to an increased CV risk in PTSD.

Influence of sympathetic nerve activity on aortic hemodynamics and pulse wave velocity in women.

Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure (P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women (P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women (P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women (P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group (P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women.NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.

Post-Exercise Neurovascular Control in Chronic Heart Failure Patients.

It remains unknown whether or not a reduction in muscle sympathetic nerve activity in heart failure patients is associated over time with the effects of long- or short-term repeated exercise. 10 chronic heart failure patients, age 49±3 years old, functional class I-III NYHA, ejection fraction <40% were randomly submitted to either an acute bout of moderate continuous exercise OR high-intensity interval exercise. Muscle sympathetic nerve activity (microneurography) and forearm blood flow (venous occlusion plethysmography) were evaluated pre- and post-exercise sessions. The moderate exercise consisted of cycle exercise at an intensity corresponding to anaerobic threshold. The interval exercise consisted of a 2-min cycle exercise at intensity corresponding to anaerobic threshold, followed by a 1-min exercise set at respiratory compensation point. Exercise capacity was evaluated by cardiopulmonary exercise test. The caloric expenditure in both sessions was 100 kcal. Baseline muscle sympathetic nerve activity and forearm blood flow levels were not different between sessions. Moderate or high-intensity exercise caused no significant changes in muscle sympathetic nerve activity and forearm blood flow. These findings suggest that the reduction in muscle sympathetic nerve activity and the increase in forearm blood flow provoked by exercise training in chronic heart failure patients are due to cumulative effects over time.