Muscle Sympathetic Nerve Activity Burst Research Articles

Sympathetic Baroreflex Sensitivity is Enhanced in Postmenopausal Women.

The sympathetic nervous system is critical for regulating blood pressure (BP) via the arterial baroreflex as well as 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 to premenopausal women (PRE). We examined beat-by-beat BP and muscle sympathetic nerve activity (MSNA) in 19 PRE (22±2 yr, 22±3 kg/m2) and 12 POST (57±5 yr, 24±2 kg/m2) during 10 minutes 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 mm Hg, P=0.43), whereas resting MSNA was elevated in POST (PRE: 10±6 vs. POST: 45±16 bursts/100 heartbeats, P<0.0001). Spontaneous sympathetic BRS was enhanced in POST (PRE: -2.0±1.2 vs. POST: -5.2±1.9 bursts/beat/mm Hg, 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.

Nadir blood pressure responses to longer consecutive cardiac cycle sequences absent of sympathetic bursts are associated with popliteal endothelial-dependent dilation

PurposeThe 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. MethodsResting 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. ResultsThe 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). ConclusionThe 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.

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.

Actigraphy-Based Sleep and Muscle Sympathetic Nerve Activity in Humans.

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 years, body mass index (BMI): 26±4 kg/m2). 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 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.

A comparison of wavelet-based action potential detection from the NeuroAmp and the Iowa Bioengineering Nerve Traffic Analysis system.

Microneurographic recordings of muscle sympathetic nerve activity (MSNA) reflect postganglionic sympathetic axonal activity directed toward the skeletal muscle vasculature. Recordings are typically evaluated for spontaneous bursts of MSNA; however, the filtering and integration of raw neurograms to obtain multiunit bursts conceals the underlying c-fiber discharge behavior. The continuous wavelet transform with matched mother wavelet has permitted the assessment of action potential discharge patterns, but this approach uses a mother wavelet optimized for an amplifier that is no longer commercially available (University of Iowa Bioengineering Nerve Traffic Analysis System; Iowa NTA). The aim of this project was to determine the morphology and action potential detection performance of mother wavelets created from the commercially available NeuroAmp (ADinstruments), from distinct laboratories, compared with a mother wavelet generated from the Iowa NTA. Four optimized mother wavelets were generated in a two-phase iterative process from independent datasets, collected by separate laboratories (one Iowa NTA, three NeuroAmp). Action potential extraction performance of each mother wavelet was compared for each of the NeuroAmp-based datasets. The total number of detected action potentials was not significantly different across wavelets. However, the predictive value of action potential detection was reduced when the Iowa NTA wavelet was used to detect action potentials in NeuroAmp data, but not different across NeuroAmp wavelets. To standardize approaches, we recommend a NeuroAmp-optimized mother wavelet be used for the evaluation of sympathetic action potential discharge behavior when microneurographic data are collected with this system.NEW & NOTEWORTHY The morphology of custom mother wavelets produced across laboratories using the NeuroAmp was highly similar, but distinct from the University of Iowa Bioengineering Nerve Traffic Analysis System. Although the number of action potentials detected was similar between collection systems and mother wavelets, the predictive value differed. Our data suggest action potential analysis using the continuous wavelet transform requires a mother wavelet optimized for the collection system.

Effect of acute intranasal insulin administration on muscle sympathetic nerve activity in healthy young adults.

Systemic insulin increases muscle sympathetic nerve activity (MSNA) via both central actions within the brainstem and peripheral activation of the arterial baroreflex. Augmented MSNA during hyperinsulinemia likely restrains peripheral vasodilation and contributes to the maintenance of blood pressure (BP). However, in the absence of insulin action within the peripheral vasculature, whether central insulin stimulation increases MSNA and influences peripheral hemodynamics in humans remains unknown. Herein, we hypothesized intranasal insulin administration would increase MSNA and BP in healthy young adults. Participants were assigned to time control [(TC), n=13 (5F/8M), 28±1 yrs] or 160 IU of intranasal insulin administered over five min [n=15 (5F/10M), 26±2 yrs]; five (1F/4M) participants completed both conditions. MSNA (fibular microneurography), BP (finger photoplethysmography), and leg blood flow (LBF, femoral Doppler ultrasound) were assessed at baseline, 15, and 30 minutes following insulin administration. Leg vascular conductance (LVC = [LBF ÷ mean BP] x 100) was calculated. Venous insulin and glucose concentrations remained unchanged throughout (p>0.05). Following intranasal insulin administration, MSNA (burst frequency; baseline = 100%; minute 15: 121±8%; minute 30: 118±6%; p=0.009, n=7) and mean BP (baseline = 100%; minute 15: 103±1%; minute 30: 102±1%; p=0.003) increased, while LVC decreased (baseline = 100%; minute 15: 93±3%; minute 30: 99±3%; p=0.03). In contrast, MSNA, mean BP, and LVC were unchanged in TC participants (p>0.05). We provide the first evidence that intranasal insulin administration in healthy young adults acutely increases MSNA and BP and decreases LVC. These results enhance mechanistic understanding of the sympathetic and peripheral hemodynamic response to insulin.

The interactive effects of posture and biological sex on the control of muscle sympathetic nerve activity during rhythmic handgrip exercise.

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 remains unknown. Thus, we tested the hypotheses that increases in muscle sympathetic nerve activity (MSNA) would be greater during upright compared to supine rhythmic handgrip (RHG) exercise, and that females would demonstrate smaller increases in MSNA during upright RHG exercise than males. Twenty young (30 [6] years; mean [SD]) individuals (9 males, 11 females) underwent 6-minutes 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 to 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 to females, that coincided with greater reductions in sympathetic baroreflex gain (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.

The Impact of Exercise Training on Muscle Sympathetic Nerve Activity: A Systematic Review and Meta-Analysis.

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], non-randomized controlled trials [non-RCTs] or pre-to-post intervention) that reported on adults (>18 years) 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]). 40 intervention studies (n=1,253 individuals) were included. RCTs of exercise compared to no exercise illustrated that those randomized to the exercise intervention had a significant reduction in MSNA burst frequency and incidence compared to controls. This reduction in burst frequency was not different between individuals with cardiovascular disease compared to those without. However, the reduction in burst incidence was greater in those with cardiovascular disease (9 RCTs studies, n = 234, MD -21.08 bursts/100 hbs; 95% CI -16.51, -25.66; I2 = 63%) compared to those without (6 RCTs, n = 192, MD -10.92 bursts/100 hbs; 95% CI -4.12, -17.73; I2 = 76%). Meta-regression analyses demonstrated a dose-response relationship where individuals with higher burst frequency and incidence pre-intervention 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.

Reflex sympathetic activation to inspiratory muscle loading is attenuated in females relative to males.

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 y) males (n=9) and females (n=7) completed two experimental days. On day one 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 and 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 (∆ 21±9 mmHg) relative to females (∆ 13±5 mmHg, p=0.026). Males also demonstrated a greater rise in MSNA burst frequency (∆ 18±7 bursts/min) relative to females (∆ 10±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.

Spontaneous Bursts of Muscle Sympathetic Nerve Activity Reduce Femoral Arterial Compliance in Humans

Previous studies in rodents have demonstrated tonic sympathetic restraint of arterial compliance. To date, studies in humans have examined sympathetic restraint of compliance via either reflexively or pharmacologically manipulating sympathetic vasoconstriction and measuring resultant changes in compliance. The extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) dynamically regulate arterial compliance in humans on a beat-by-beat basis remains unknown. Herein, we hypothesized that femoral arterial compliance would be transiently reduced following spontaneous bursts of MSNA. Further, we hypothesized that the magnitude of reduction in arterial compliance would be graded to the MSNA burst amplitude (index of net neural outflow). Beat-to-beat blood pressure (BP; Finometer), heart rate (ECG), MSNA (peroneal microneurography), and femoral artery blood flow (duplex Doppler ultrasound) were continuously measured over 10-20 minutes of quiet supine rest in 27 young, healthy men (age: 22 ± 1 years, resting MSNA burst frequency: 11 ± 5 bursts/minute). Customized labview programs were used to time-align neural cardiovascular variables with ultrasound data sampled at 30Hz, enabling the quantification of arterial compliance on a beat-by-beat basis defined as the change in arterial cross-sectional area divided by the change in blood pressure over the cardiac cycle. Bursts of MSNA were tracked for 10 cardiac cycles and changes in arterial compliance were quantified using signal-averaging for all bursts, and subsequently, for bursts of MSNA when sub-classified based on amplitude into quartiles (Q1= smallest 25% of bursts, Q4= largest 25% of bursts). Reductions in arterial compliance were significantly greater following cardiac cycles with bursts of MSNA compared to cardiac cycles without bursts of MSNA (bursts: -5.1 ± 0.6% vs. non-bursts: -0.8 ± 0.2%, p&lt;0.001). Further, reductions in compliance appeared to be graded to MSNA burst amplitude (Q1: -6.5 ± 0.8%; Q4: -9.1 ± 1.3%, P=0.051). The latency (i.e., number of heartbeats) to nadir arterial compliance following bursts of MSNA was 4.2 ± 0.6 cardiac cycles. Collectively, these findings suggest that the sympathetic nervous system dynamically regulates femoral arterial compliance on a beat-to-beat basis. College of Nursing and Health Innovation, University of Texas at Arlington. 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.

Older versus Younger Females Matched for Body Composition Have Lower Sympathetic Transduction at Rest

BACKGROUND: Older female (OF) adults have the highest risk for hypertension and cardiovascular disease among any demographic in America. Therefore, there is a need to better understand the contributors to impaired blood pressure (BP) regulation in female aging. Bursts of spontaneously occurring muscle sympathetic nerve activity (MSNA) contribute to BP regulation on a beat-to-beat basis (i.e., sympathetic transduction). Previous work suggests that OF have attenuated resting sympathetic transduction but there is a need for additional work considering covariates that affect sympathetic transduction (e.g., body mass index (BMI) &amp; sodium intake). We tested the hypothesis that aging attenuates sympathetic transduction in OF (&gt;55 years) compared with young female (YF; 18-35 years) participants matched for body composition and pre-trial sodium intake. METHODS: We studied seven post-menopausal OF (65±6 years) and nine YF (24±4 years; tested in early follicular phase) participants with seated brachial BP &lt;140/90 mmHg after three days of specified sodium intake (target 2300mg/day). We measured mean BP (photoplethysmography) and MSNA (microneurography) during a 10-min rest period in the supine position. We also assessed BMI, body fat % (BF%; bioelectrical impedance), and habitual moderate-to-vigorous physical activity (MVPA) during ≥7 consecutive days using waist-worn accelerometers (ActiGraph). We compared the average change in BP for 10 cardiac cycles after an MSNA burst (i.e., signal-averaged sympathetic transduction) using mixed-effects models (group*time[repeated measure]). We compared other variables using unpaired, two-tailed t-tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data (i.e., failed Shapiro-Wilk test). We compared sodium intake, BMI, BF% and MVPA using equivalence testing. Significance was set to α&lt;0.05. RESULTS: Sodium intake, BMI, BF% and MVPA were equivalent between groups (p&gt;0.06). The following data are presented as OF vs. YF with mean ± SD or median[IQR]. Mean BP (97[22] vs. 77[5] mmHg, p=0.008) and MSNA burst frequency (35±6 vs. 13±4 bursts/min, p&lt;0.0001) were higher in OF. OF had lower mean BP changes following MSNA bursts (time: p&lt;0.0001, group: p=0.013, interaction: p=0.026) with pairwise differences among cardiac cycles 4-10 (post hoc p-values: p≤0.012). Moreover, peak increases in mean BP following MSNA bursts were lower in OF (Δ1.9±0.4 vs. 4.9±2.2 mmHg, p=0.003). CONCLUSION: We found that OF have attenuated sympathetic transduction to BP when compared to YF matched for body composition and sodium intake. This extends past work suggesting that female aging is associated with attenuated sympathetic transduction to BP. National Institutes of Health K01HL160772 (JCW), American Heart Association 23CDA1037938 (JCW), &amp; Florida State University Graduate School Legacy Fellowship, 2023 (CD). 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.

Young Trauma-Exposed Women with Low Sleep Effciency have Blunted Sympathetic Baroreflex Sensitivity and Higher Muscle Sympathetic Nerve Activity

Introduction: Poor sleep, a known risk factor for cardiovascular disease (CVD) and one of the American Heart Association’s essential 8th, is common after trauma-exposure. Although premenopausal women are thought to be protected from CVD, trauma exposure might increase their CVD risk. In a recent large epidemiological study examining sleep-related CVD comorbidities, the empirical cut off point for optimal sleep effciency (SE) was set at 83%, distinguishing between good and poor sleep effciency. Studies have suggested an overactive sympathetic nervous system and an impaired baroreflex sensitivity (BRS) as potential mechanisms of increased CVD risk. However, the impact of poor sleep effciency on muscle sympathetic nerve activity (MSNA) and BRS in young trauma-exposed women is unknown. We hypothesized that young trauma-exposed women with poor sleep effciency will present with impaired BRS and increased MSNA at rest. Methods: We collected data on 30 women (18 – 40 years) from diverse backgrounds who had been exposed to trauma. Sleep data was acquired via ActiWatch for 7 days and used to categorize our participants into two groups: good effciency (SE &gt; 83%, n=17) and poor effciency (SE &lt; 83%, n=13), with SE calculated as the percentage of time spent asleep while in bed. Additionally, we collected continuous noninvasive blood pressure (BP), heart rate (HR), and MSNA (burst frequency, incidence, and total activity) during 10 minutes of quiet rest. Sympathetic BRS was determined as the slope of the regression between individual sympathetic bursts and diastolic BP bins (3 mmHg), weighted against the number of cardiac cycles, utilizing an automated program (Ensemble, NZ). Results: There were no significant differences in trauma symptom severity, resting BP and HR between the two groups (p&gt;0.05 for all). However, resting sympathetic BRS was blunted in the poor SE (-0.10±0.88 bursts/100hb/mmHg) compared to the good SE (-1.44±1.58 bursts/100hb/mmHg, p=0.006) group, even after adjusting for age (p=0.009). Likewise, resting total MSNA was higher in the poor SE compared to the good SE after adjusting for age (p=0.028). MSNA burst frequency and burst incidence were comparable between the groups (p&gt;0.05). Conclusion: Our analyses revealed that poor sleep effciency is associated with decreased sympathetic baroreflex sensitivity and higher total muscle sympathetic activity at rest, regardless of age. Blunted sympathetic BRS may contribute to increased sympathetic activity in young women with poor sleep effciency. Future studies testing strategies to improve sleep effciency in this population could provide potential long-term cardiovascular benefits. UL1TR002494 and NIH K01HL161027 No disclosure. 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.

Ganglionic blockade modulates sympathetic neural discharge and neurocirculatory regulation in humans

This study investigated the impact of integrated muscle sympathetic nerve activity (MSNA) discharge patterns on human neurocirculatory regulation. In 13 healthy females (42 ± 15 years), the transduction of integrated MSNA (peroneal microneurography) into mean arterial pressure (MAP; arterial catheter) was studied during an intravenous infusion of a nicotinic ganglionic antagonist (trimethaphan camsylate, 1-7 mg/min). Neurovascular transduction (signal averaging) was studied based on the overall response, burst sequence (singlet, doublet, and triplet+), and burst amplitude (binned into tertials: small, medium, and large bursts). Data (mean ± SD) are reported for a 10-minute baseline (BSL), the one-minute period at the midpoint of the trimethaphan infusion with integrated MSNA bursts (TM-Mid), and the last minute of trimethaphan infusion with integrated MSNA bursts (TM-Last). During BSL, the MAP transduction responses were greatest for triplets+ (singlets: 0.9 ± 0.2 mmHg, doublets: 2.0 ± 0.6 mmHg, triplet+: 2.6 ± 0.9 mmHg; P &lt; 0.01) and large bursts (small: 1.0 ± 0.3 mmHg, medium: 1.7 ± 0.5 mmHg, large: 2.2 ± 0.7 mmHg; P &lt; 0.01). Trimethaphan infusion reduced integrated MSNA burst frequency resulting in a greater proportion of singlets (BSL: 45 ± 18 %, TM-Mid: 75 ± 23 %, TM-Last: 94 ± 20 %; P &lt; 0.01), a lower proportion of doublets, and a lower proportion of triplets+ (BSL: 23 ± 19 %, TM-Mid: 9 ± 18 %, TM-Last: 0 ± 0 %; P &lt; 0.01). Trimethaphan infusion reduced integrated MSNA burst amplitude resulting in a greater proportion of small bursts (BSL: 33 ± 0.2 %, TM-Mid: 60 ± 26 %, TM-Last: 78 ± 37 %; P &lt; 0.01), a lower proportion of medium bursts, and a lower proportion of large bursts (BSL: 34 ± 1 %, TM-Mid: 17 ± 26 %, TM-Last: 1 ± 5 %; P &lt; 0.01). Trimethaphan-mediated changes in MSNA burst frequency and amplitude were associated with reduced overall MAP transduction responses (BSL: 1.6 ± 0.5 mmHg, TM-Mid: 0.5 ± 0.2 mmHg, TM-Last: 0.3 ± 0.3 mmHg; P &lt; 0.01). Linear regression analyses demonstrated that the trimethaphan-mediated reduction in the proportion of large bursts ( β = 0.02 ± 0.008 mmHg/%, R2 = 0.13, P = 0.03) more strongly affected sympathetic neurovascular transduction responses than reductions in the proportion of triplet+ burst sequences (P = 0.91). These findings suggest that time varying MSNA discharge patterns, particularly variations in burst amplitude, support human neurocirculatory regulation. This work was supported by the National Institutes of Health and the Natural Sciences and Engineering Research Council of Canada. 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.

Respiratory Modulation of Muscle Sympathetic Nerve Activity in Type 2 Diabetes Mellitus

Dysfunctional sympathetic neural regulation is present in patients with type 2 diabetes (T2D) with augmented muscle sympathetic nerve activity (MSNA) responses to handgrip exercise, cold pressor testing, and augmented sympathetic-blood pressure transduction identified. MSNA is modulated by respiration such that it is inhibited at higher lung volumes and increased at lower lung volumes. Herein we aimed to determine whether T2D affects the respiratory modulation of MSNA. Resting MSNA (microneurography) and respiration pattern (strain-gauge pneumobelt) were measured simultaneously in 20 patients with T2D (age 49.1±7.4 years, body mass index [BMI] 31.9±4.1 kg∙m−2, mean ± SD) and 13 age- and BMI-matched, healthy controls (46.3±9.4 years; 32.1±4.6 kg∙m−2). MSNA was stratified by the phase of respiration. Further comparisons were made between low lung volume (defined as 60-100% expiration + 0-60% inspiration) and high lung volume states (60-100% inspiration + 0-60% expiration). Resting MSNA burst frequency, burst incidence and total activity were similar between T2D and controls (p=0.953, p=0.624, and p=0.884, respectively). Both groups exhibited peak MSNA in late expiration to early inspiration, whilst inhibition of MSNA occurred during late inspiration to early expiration (respiratory phase p&lt;0.001 for burst frequency, incidence and total activity), though no group x respiratory phase interaction was observed (p&gt;0.05 for all MSNA measures). When MSNA responses were compared between lung volume states, percent reduction of MSNA burst incidence from low lung volume to high lung volume was less in T2D than controls (26.1±33.9 vs 50.1±25.6%, p=0.025). Furthermore, in T2D, there was a shift in the distribution of MSNA bursts with a greater proportion of bursts occurring at high lung volumes (i.e., burst count during high lung volume divided by total burst count) compared to controls (43.8±10.5 vs. 37.8±12.5% respectively, group x volume interaction p=0.04). Notably, the normal pattern of respiratory modulation of MSNA was absent in 5 T2D patients (non-modulators), whilst this did not occur in any control participants. Non-modulators had higher systolic blood pressure compared to modulators (138.7±16.6 vs. 123.2±10.6 mmHg respectively, p=0.024), with no differences in age, BMI, HbA1c, duration of T2D, or overall MSNA parameters (all p&lt;0.05). These results suggest that whilst respiratory modulation of MSNA occurs in T2D, its effect appears blunted compared to healthy controls. Notably, the usual pattern of respiratory-sympathetic coupling is absent in some T2D patients, which may be associated with higher resting systolic blood pressure. MP is supported by the Greenlane Research and Educational Fund (21/01/4153). 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.

Spontaneous Sympathetic Baroreflex Sensitivity Is Impaired in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have chronic overactivation of the sympathetic nervous system that contributes to hypertension and increased cardiovascular risk. The sympathetic baroreflex is a major regulator of sympathetic activity in response to changes in blood pressure; however, limited information is available regarding sympathetic baroreflex control in non-dialysis patients with CKD. In the present study we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) is attenuated in non-dialysis patients with CKD. In 17 sedentary patients with CKD stages III-IV (76% hypertensive and 29% with diabetes) [12 male/5 female, age: 57 ± 13 yr, 13 Black/4 White, systolic/diastolic BP: 122 ± 17/75 ± 7 mmHg, BMI: 31 ± 5 kg/m2, eGFR: 40 ± 14 mL/min/1.73m2] and 9 controls (CON) (89% hypertensive and 22% with diabetes) [7 male/2 female, age: 51 ± 13 yr, 8 Black/1 White, systolic/diastolic BP: 123 ± 6/79 ± 6 mmHg, BMI: 30 ± 6 kg/m2, eGFR: 95 ± 12 mL/min/1.73m2], resting beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA, microneurography) were continuously recorded during 10 min of semi-recumbent rest. Weighted linear regression analysis between MSNA burst incidence and diastolic blood pressure was used to determine the spontaneous sympathetic baroreflex sensitivity (sBRS). Resting MSNA burst incidence was higher in patients with CKD [CKD: 70 ± 19 bursts (100 heart beats)−1. mmHg−1 versus CON: 47 ± 9 bursts (100 heart beats)−1. mmHg−1; p&lt;0.001], and a higher MSNA burst frequency was observed in CKD (CKD: 43 ± 11 bursts. min−1 versus CON: 32 ± 10 bursts. min−1; P=0.021], whereas resting mean arterial blood pressure (91 ± 9 mmHg versus 94 ± 5 mmHg; P=0.317) and heart rate were similar between groups. Patients with CKD had reduced sBRS compared to controls [CKD: -1.37 ± 0.59 bursts (100 heart beats)−1 mmHg−1 versus CON: -2.79 ± 1.33 bursts (100 heart beats)−1 mmHg−1; P=0.013]. The MSNA burst incidence (r = -0.63, p&lt;0.001) and the sBRS (r = -0.57, P=0.002) were significantly associated with the estimated glomerular filtration rate (eGFR). Overall, these preliminary findings suggest an attenuated sympathetic baroreflex sensitivity in patients with CKD compared with age and-comorbidities matched controls, with greater impairment in those with more severe kidney dysfunction. This work was supported by National Institutes of Health Grants R01HL135183 and R61AT010457 (J.P). 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.

Neural-Cardiovascular Responses to Orthostasis Following 8-Weeks of Home-Based Lower Leg Heating in Older Women with Hypertension

Background: Hypertension remains a significant health problem for older women (≥60 y). Though effective blood pressure (BP) interventions exist (e.g., exercise, medication), adherence to these options is low. Lower leg heat therapy represents a promising and easily implementable adjuvant treatment that may offer cardioprotective benefits. However, no studies have investigated lower leg heat therapy’s effects on BP and neural-cardiovascular function, let alone in older women with hypertension. Accordingly, we hypothesized that 8-weeks of home-based lower leg heat therapy in older women with hypertension would 1) reduce ambulatory BP and 2) reduce muscle sympathetic nerve activity (MSNA) while augmenting cardiac output and stroke volume during graded head-up tilt (HUT). Methods: Forty older women with hypertension (69 ± 5 y [mean±SD]) were randomized to either heat therapy (INT, 42°C; n = 20) or a thermoneutral control (CON, 35°C; n = 20). Each woman completed 8 wks of at-home sessions (~4/wk; 45 min/session) immersing their legs ~33 cm in a portable spa bath. 24-h ambulatory BP was measured pre- (PRE) and post-intervention (POST). A subset of women (n = 18 for each group) completed supine rest and 5 min of 30° and 60° HUT at each time point, whereby laboratory heart rate, systolic and diastolic BP, MSNA burst frequency and incidence (microneurography), cardiac output (acetylene rebreathing), and stroke volume (cardiac output/heart rate) were measured. Results: Between INT and CON, PRE ambulatory awake systolic BP (140 ± 7 vs. 142 ± 6 mmHg; P = 0.34) and diastolic BP (80 ± 6 vs. 79 ± 6 mmHg; P = 0.51) were not different, nor were PRE supine systolic BP, diastolic BP, or heart rate (all P &gt; 0.05). PRE supine resting MSNA burst frequency (36 ± 13 vs. 33 ± 16 bursts/min), MSNA burst incidence (54 ± 19 vs. 51 ± 22 bursts/100 heartbeats), cardiac output (4.9 ± 0.9 vs. 5.1 ± 1.0 L/min), and stroke volume (72 ± 15 vs. 76 ± 15 mL/beat) were not different between groups (all P &gt; 0.05). From PRE to POST neither ambulatory awake systolic nor diastolic BP differed between groups (all P &gt; 0.05). Despite this, POST laboratory systolic and diastolic BP were greater in INT (both P &lt; 0.05) but not in CON (both P &gt; 0.05) during HUT. POST laboratory heart rate was reduced in INT ( P = 0.025), and trended greater in CON ( P = 0.065) across HUT. Neither MSNA burst frequency nor burst incidence changed during HUT PRE to POST (all P &gt; 0.05). Despite no PRE to POST differences in cardiac output in either group (all P &gt; 0.05), INT had a greater overall POST stroke volume throughout HUT ( P = 0.011), while CON had a reduced stroke volume during 60° HUT ( P = 0.036). Conclusions: Contrary to our hypotheses, 8-weeks of home-based lower leg heat therapy did not improve ambulatory BP or HUT MSNA and cardiac output in older women with hypertension. However, women completing INT appeared to have a greater stroke volume and lower heart rate during HUT. Accordingly, these data suggest that 8-weeks of lower leg heat therapy in older women with hypertension may improve cardiac function during orthostasis without significant changes in sympathetic outflow or ambulatory BP. Supported by the National Institutes of Health (R01AG059314 and F32HL167556). 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.

Antioxidant-induced modulation of sympathetic transduction to arterial blood pressure in humans

Purpose: Excess plasma free fatty acids (FAA) promote oxidative stress and an increase in peripheral resistance. Therefore, we tested the hypothesis that excess FAA limits sympathetic control of arterial blood pressure (BP) and that sympathetic control would be restored during co-administration of ascorbic acid, which is an antioxidant with vasodilatory properties. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 5 lean, healthy adults with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Sympathetic control of BP was examined by determining the BP response to individual bursts of muscle sympathetic nerve activity (MSNA) (microneurography). Briefly, beat-to-beat mean arterial pressure (MAP) was measured continuously (finger cuff) and signal-averaged over 15 cardiac cycles following each detected burst of MSNA over a 10-min resting period. Results: In contrast to our hypothesis, no change was observed in sympathetic transduction during lipid infusion (1.5 ± 0.4 vs. 1.4 ± 3 mmHg, P=0.75). However, co-infusion of ascorbic acid significantly increased sympathetic transduction compared with baseline (1.5 ± 0.4 vs. 2.0 ± 3 mmHg, P=0.04), in addition to reducing peripheral resistance (0.73 ± 0.11 vs. 0.53 ± 12 mmHg·min·mL−1, P=0.07). MSNA and MAP were not significantly changed during the 2-hr infusions. Conclusions: These preliminary findings suggest that excess FAA do not modulate sympathetic transduction in lean, healthy adults. However, ascorbic acid infusion reduces peripheral resistance and increases sympathetic transduction, demonstrating an inverse relation between peripheral resistance and sympathetic transduction in healthy adults. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366) The contents are solely the responsibility of the authors and do not necessarily represent the offcial views of the NIH or NCATS. 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.

Interactions Between Reproductive Hormones and Neuro-Vascular Regulation During the Cold Pressor Test in Young Females

Recently, we reported that muscle sympathetic nerve activity (MSNA) is not predictive of vascular nor blood pressure outcomes during the cold pressor test (CPT) in young healthy females. Instead, we observed substantial variability in vascular responses to the CPT which ranged widely from decreases in blood flow and vascular conductance to increases in these same outcomes. Interindividual differences in circulating reproductive hormones may account for this female-specific variability in vascular responses to acute elevations in MSNA. Therefore, the purpose of this study was to test the hypothesis that reproductive hormones account for variability in MSNA, femoral blood flow (FBF), and femoral vascular conductance (FVC) during the CPT in females. We retrospectively assessed data from 9 young healthy females (age: 24±3 years) in the low hormone phase of their menstrual cycle (days 1-5). Intravenous blood samples were obtained and prospectively analyzed to assess concentrations of circulating reproductive hormones (radioimmunoassay). Integrated peroneal MSNA (microneurography; NeuroAmpEX, ADI) was quantified at rest and during a 3-minute hand CPT. Mean arterial pressure (MAP) was measured beat-by-beat (Finometer Midi, FMS) and duplex vascular ultrasound was used to measure FBF; FVC was quantified as FBF/MAP (mL/min/mmHg). All variables are expressed as the difference between the average CPT value and the average baseline value. CPT-induced changes in MSNA burst incidence (bursts/100hb) were not related to [17-beta-estradiol] (R2=0.05; P=0.60), [progesterone] (R2=0.11, P=0.47), or [free testosterone] (R2=0.01, P=0.81). Similarly, changes in FBF and FVC were not related to [17-beta-estradiol] (FBF: R2=0.04, P=0.67; FVC: R2=0.01, P=0.80) or [progesterone] (FBF: R2=0.04, P=0.67; FVC: R2=0.09, P=0.51). However, there was a negative correlation between [free testosterone] and the changes in both FBF (R2=0.69, P=0.02) and FVC (R2=0.66, P=0.03). In other words, females with higher free testosterone demonstrated larger decreases in FBF and FVC during the CPT relative to those with lower free testosterone concentrations. These data suggest that circulating free testosterone may act to increase the vasoconstrictive consequences of MSNA in females, and may account for the previously observed variability in vascular responses to MSNA during acute stress. This project was funded by: NSERC and FRQ-S. 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.

Intra- and interday reliability of sympathetic transduction to blood pressure in young, healthy adults.

Microneurographic recordings of muscle sympathetic nerve activity (MSNA) and the succeeding changes in beat-to-beat blood pressure (i.e., sympathetic transduction) provide important insights into the neural control of the circulation in humans. Despite its widespread use, the reliability of this technique remains unknown. Herein, we assessed the intra- and interday test-retest reliability of signal-averaging sympathetic transduction to blood pressure. Data were analyzed from 15 (9 M/6 F) young, healthy participants who completed two baseline recordings of fibular nerve MSNA separated by 60 min (intraday). The interday reliability was obtained in a subset of participants (n = 13, 9 M/4 F) who completed a follow-up MSNA study. Signal-averaging sympathetic transduction was quantified as peak change in diastolic (DBP) and mean arterial pressure (MAP) following a burst of MSNA. Analyses were also computed considering different MSNA burst sizes (quartiles of normalized MSNA) and burst patterns (singlets, couplets, triplets, and quadruplets+), as well as nonburst responses. Intraclass-correlation coefficients (ICCs) were used as the main reliability measure. Peak changes in MAP [intraday: ICC = 0.76 (0.30-0.92), P = 0.006; interday: ICC = 0.91 (0.63-0.97), P < 0.001] demonstrated very good to excellent reliability. Sympathetic transduction of MSNA burst size displayed moderate to very good reliability, though the reliability of MSNA burst pattern was poor to very good. Nonburst responses revealed poor intraday [ICC = 0.37 (-1.05 to 0.80), P = 0.21], but very good interday [ICC = 0.76 (0.18-0.93), P = 0.01] reliability. Intraday reliability measures were consistently lower than interday reliability. Similar results were obtained using DBP. Collectively, these findings provide evidence that the burst-triggering signal-averaging technique is a reliable measure of sympathetic transduction to blood pressure in young, healthy adults.NEW & NOTEWORTHY We found that signal-averaging sympathetic transduction to blood pressure displayed very good to excellent intra- and interday test-retest reliability in healthy, young adults. Reliability analyses according to muscle sympathetic burst size, burst pattern, and nonburst response were less consistent. Results were similar when using diastolic or mean arterial pressure in the transduction calculation. These findings suggest that the signal-averaging technique can be used with confidence to investigate sympathetic transduction to blood pressure in humans across time.