Post-exercise Circulatory Occlusion Research Articles

Descending motor drive does not interact with muscle metaboreflex for ventilation regulation during rhythmic exercise in healthy humans.

The muscle metaboreflex effect on pulmonary ventilation (V̇E) regulation is more apparent during rhythmic exercise than rest, possibly because this reflex interacts with other mechanisms regulating V̇E during voluntary contractions, such as central command. Therefore, we tested whether one part of central command, the descending component of motor execution (i.e., descending motor drive), and the muscle metaboreflex interact synergistically to regulate V̇E. Thirteen healthy adults (9 men) completed four experiments in random order under isocapnia. The muscle metaboreflex was activated by rhythmic handgrip exercise at 60% maximal voluntary contraction (MVC) force with the dominant hand. Then, the muscle metaboreflex remained active during a 4-minute recovery period via post-exercise circulatory occlusion (PECO), or it was inactivated, maintaining free blood flow to the dominant upper limb. During the last 2-minutes of the handgrip exercise recovery, participants either performed rhythmic voluntary plantar flexion with the dominant leg at 30% MVC torque to generate descending motor drive or the dominant leg's calf muscles were involuntarily activated by electrical stimulation at a similar torque level (i.e., without descending motor drive). V̇E increased to a similar level during handgrip exercise in all conditions (≈22 L/min, P = 0.364). PECO maintained V̇E elevated above recovery with free blood flow (≈17 L/min vs. ≈13 L/min, P = 0.009). However, voluntary and involuntary plantar flexion with or without PECO evoked similar V̇E responses (∆ ≈ 4 L/min, P = 0.311). Therefore, an interaction between descending motor drive and muscle metaboreflex is not ubiquitous for V̇E regulation during rhythmic exercise.

Consideration of absolute intensity when examining sex differences in blood pressure responses during static exercise.

Low- to moderate-intensity submaximal static contractions are commonly used to study the effects of biological sex on the cardiovascular response to exercise. Under this paradigm, premenopausal females frequently demonstrate smaller blood pressure responses than age-matched males. These differences are preserved during postexercise circulatory occlusion, implicating the muscle metaboreflex as an important driver of sex differences in the blood pressure response to static exercise. The mechanisms responsible for these differences are incompletely understood but often attributed to innate sex differences in skeletal muscle fiber type distribution, muscle metabolism, and/or sympathetic control of the circulation. However, one potential confounding factor is that the majority of studies use relative intensity exercise (e.g., 30% of maximal voluntary contraction), such that on average, females are completing static contractions at a lower absolute intensity. In this review, we summarize human evidence showing that sex differences in blood pressure responses to static exercise are attenuated or abolished when controlling for absolute intensity and muscle strength, either by statistical methods or strength-matched cohorts. We highlight evidence that the effect of higher absolute contraction intensity on exercise blood pressure likely occurs through increased mechanical occlusion of skeletal muscle microvasculature, leading to greater activation of the muscle metaboreflex. These findings highlight an important need to account for absolute intensity when studying and interpreting sex differences in cardiovascular responses to exercise.

Effect of a new resistance training method on the metaboreflex in cardiac rehabilitation patients: a randomized controlled trial.

Patients with cardiac disease exhibit exaggerated sympathoexcitation, pressor, and ventilatory responses to muscle metaboreflex activation (MMA). However, the effects of cardiac rehabilitation (CR) and especially resistance training (RT) modalities on MMA are not well known. This study investigated how CR impacts MMA in such patients, specifically examining the effects of two different resistance training (RT) protocols following 12weeks of CR. In addition to endurance exercises, 32 patients were randomized into either a 3/7 RT modality (comprising 5 sets of 3-7 repetitions) or a control (CTRL) modality (involving 3 sets of 9 repetitions), with distinct inter-set rest intervals (15s for 3/7 and 60s for CTRL). MMA, gauged by blood pressure (BP) and ventilatory (Ve) responses during a handgrip exercise at 40% effort and subsequent post-exercise circulatory occlusion, demonstrated CR's significant impact. Systolic BP, initially at + 28 ± 23% pre-CR, improved to + 11 ± 15% post-CR (P = .011 time effect; P = .131 group effect). Diastolic BP showed a similar trend, from + 27 ± 23% to + 13 ± 15% (P = .099 time effect; P = .087 group effect). Ve, initially at + 60 ± 39%, reduced to + 14 ± 19% post-CR (P < .001 time effect; P = .142 group effect). Critical parameters-maximal oxygen consumption, lean mass, hand grip, and quadriceps strength-exhibited parallel increases in both 3/7 and CTRL groups (P < .05 time effect; P > .3 group effect). Ultimately, CR demonstrated comparable improvements in MMA across both RT modalities, indicating its positive influence on cardiovascular responses and physical performance in individuals with cardiac conditions.

Influence of endogenous and exogenous hormones on the cardiovascular response to lower extremity exercise and group III/IV activation in young females.

Oral contraceptive (OC) use can increase resting blood pressure (BP) in females as well as contribute to greater activation of group III/IV afferents during upper body exercise. It is unknown, however, whether an exaggerated BP response occurs during lower limb exercise in OC users. We sought to elucidate the group III/IV afferent activity-mediated BP and heart rate responses while performing lower extremity tasks during early and late follicular phases in young, healthy females. Females not taking OCs (NOC: n = 8; age: 25 ± 4 yr) and those taking OCs (OC: n = 10; age: 23 ± 2 yr) completed a continuous knee extension/flexion passive stretch (mechanoreflex) and cycling exercise with subsystolic cuff occlusion (exercise pressor reflex), which was followed by a 2-min postexercise circulatory occlusion (PECO) (metaboreflex). Data collection occurred on two occasions: once during the early follicular phase (days 1-4) and once during the late follicular phase (days 10-14) of their menstrual cycle (NOC) or during the placebo and active pill phases (OC). Resting mean arterial BP and heart rate were not different between phases in NOC and OC participants (P > 0.05). Hemodynamic responses to metaboreflex, mechanoreflex, and collective exercise pressor reflex activation were not different between phases in both groups (P > 0.05). In conclusion, although OCs are known to increase BP at rest, our findings indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during large, lower limb muscle exercise with or without group III/IV afferent activation in young, healthy females.NEW & NOTEWORTHY Sex differences in the cardiovascular response to exercise have been demonstrated and may be dependent on sex hormone levels. Furthermore, oral contraceptives (OCs) have been shown to exaggerate the blood pressure response to upper extremity exercise. The results of this study indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during lower extremity dynamic exercise or with group III/IV afferent activation in young, healthy females.

Central motor output does not interact with muscle metaboreceptors input for ventilation regulation during dynamic exercise in health humans

INTRODUCTION: The muscle metaboreflex typically does not contribute to ventilation regulation when activated in isolation at rest via post-exercise circulatory occlusion (PECO), but it might synergistically interact with other mechanisms operating during voluntary exercise. Efferent signals from brain areas involved in the motor control of appendicular skeletal muscles to the medulla (i.e., central command) supposedly contribute to ventilation regulation during voluntary exercise. Therefore, we sought to test the hypothesis that central motor output interacts with muscle metaboreceptor input, generating a greater ventilatory response to PECO during voluntary exercise than electrically-induced involuntary exercise. METHODS: Thirteen healthy adults (4 women, age: 26 ± 5 years) participated in the study. Each participant completed four experiments in random order. Two experiments were accomplished per visit at 30-minute intervals. The interval between visits was at least two and at most seven days. The muscle metaboreflex was activated by rhythmic handgrip exercise with the dominant hand at 60% of the maximal voluntary contraction force with a 2-s duty cycle. Then, the muscle metaboreflex remained active for a 4-minute recovery period via PECO, or it was inactivated via free circulation to the exercised arm. During the last 2-minutes of the handgrip exercise recovery, participants either performed unilateral voluntary plantar flexion with the dominant leg to generate central motor output or the dominant leg’s calf was involuntarily activated by electrical stimulation not to have central motor output. Voluntary and involuntary calf contractions were performed at the same external workload. A rebreathing circuit maintained isocapnia throughout all experiments. A bidirectional turbine measured breath-by-breath airflow. Heart rate was measured via ECG, and arterial pressure by auscultation in a resting arm. RESULTS: Ventilation, heart rate, and arterial pressure increased during handgrip exercise similarly in all experiments. PECO-induced muscle metaboreflex activation maintained ventilation (Δ = 5.4 ± 5.2 l/min, P = 0.003), heart rate (Δ = 6.6 ± 8.0 bpm, P = 0.011) and systolic arterial pressure (Δ = 28.4 ± 14.8 mmHg, P &lt; 0.001) elevated above the control handgrip exercise recovery with free circulation to the exercised arm. The ventilation response to voluntary plantar flexion was greater when PECO was present in the arm than when it was absent (Δ = 8.3 ± 5.6 l/min vs. 4.5 ± 2.7 l/min, P = 0.006), reproducing previous findings. However, the ventilation response to voluntary and involuntary plantar flexion with a PECO background was similar (Δ = 8.3 ± 5.6 l/min vs. 8.2 ± 6.3 l/min, P = 1.000). CONCLUSION: The data do not support that an interaction between central motor output and muscle metaboreceptors input is obligatory to generate a ventilatory response to PECO during voluntary exercise. FINANCIAL SUPPORT: grant 2023/07135-0, São Paulo Research Foundation (FAPESP); Scientific production award from the National Council for Scientific and Technological Development (CNPq; Process: 310110/2019-0). 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.

Acute isometric and dynamic exercise do not alter cerebral sympathetic nerve activity in healthy humans

The impact of physiological stressors on cerebral sympathetic nervous activity (SNA) remains controversial. We hypothesized that cerebral noradrenaline (NA) spillover, an index of cerebral SNA, would not change during both submaximal isometric handgrip (HG) exercise followed by a post-exercise circulatory occlusion (PECO), and supine dynamic cycling exercise. Twelve healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and right internal jugular vein. Right internal jugular vein blood flow was measured using Duplex ultrasound, and tritiated NA was infused through the participants' right superficial forearm vein. Heart rate was recorded via electrocardiogram and blood pressure was monitored using the right radial artery. Total NA spillover increased during HG (P = 0.049), PECO (P = 0.006), and moderate cycling exercise (P = 0.03) compared to rest. Cerebral NA spillover remained unchanged during isometric HG exercise (P = 0.36), PECO after the isometric HG exercise (P = 0.45), and during moderate cycling exercise (P = 0.94) compared to rest. These results indicate that transient increases in blood pressure during acute exercise involving both small and large muscle mass do not engage cerebral SNA in healthy humans. Our findings suggest that cerebral SNA may be non-obligatory for exercise-related cerebrovascular adjustments.

Altered locomotor muscle metaboreflex control of ventilation in patients with COPD.

We investigated the locomotor muscle metaboreflex control of ventilation, circulation, and dyspnea in patients with chronic obstructive pulmonary disease (COPD). Ten patients [forced expiratory volume in 1 second (FEV1; means ± SD) = 43 ± 17% predicted] and nine age- and sex-matched controls underwent 1) cycling exercise followed by postexercise circulatory occlusion (PECO) to activate the metaboreflex or free circulatory flow to inactivate it, 2) cold pressor test to interpret whether any altered reflex response was specific to the metaboreflex arc, and 3) muscle biopsy to explore the metaboreflex arc afferent side. We measured airflow, dyspnea, heart rate, arterial pressure, muscle blood flow, and vascular conductance during reflexes activation. In addition, we measured fiber types, glutathione redox balance, and metaboreceptor-related mRNAs in the vastus lateralis. Metaboreflex activation increased ventilation versus free flow in patients (∼15%, P < 0.020) but not in controls (P > 0.450). In contrast, metaboreflex activation did not change dyspnea in patients (P = 1.000) but increased it in controls (∼100%, P < 0.001). Other metaboreflex-induced responses were similar between groups. Cold receptor activation increased ventilation similarly in both groups (P = 0.46). Patients had greater type II skeletal myocyte percentage (14%, P = 0.010), lower glutathione ratio (-34%, P = 0.015), and lower nerve growth factor (NGF) mRNA expression (-60%, P = 0.031) than controls. Therefore, COPD altered the locomotor muscle metaboreflex control of ventilation. It increased type II myocyte percentage and elicited redox imbalance, potentially producing more muscle metaboreceptor stimuli. Moreover, it decreased NGF expression, suggesting a downregulation of metabolically sensitive muscle afferents.NEW & NOTEWORTHY This study's integrative physiology approach provides evidence for a specific alteration in locomotor muscle metaboreflex control of ventilation in patients with COPD. Furthermore, molecular analyses of a skeletal muscle biopsy suggest that the amount of muscle metaboreceptor stimuli derived from type II skeletal myocytes and redox imbalance overcame a downregulation of metabolically sensitive muscle afferents.

The human skeletal muscle metaboreflex contribution to cardiorespiratory control in males and females in dynamic exercise.

There is a significant effect of sex and muscle mass on the cardiorespiratory response to the skeletal muscle metaboreflex during isometric exercise. We therefore tested the hypothesis that sex differences would be present when isolated following dynamic exercise. We also tested the hypothesis that single and double leg post-exercise circulatory occlusion (PECO) following heavy exercise would elicit a cardiorespiratory response proportional to the absolute muscle mass. Healthy (24±4 years) males (n=10) and females (n=10) completed pulmonary function and an incremental cycle test to exhaustion. Participants completed two randomized, 6 min bouts of intense cycle exercise (84±7% V̇O2peak). One exercise bout was immediately followed by 3 min PECO (220mmHg) of the legs while the other exercise bout was followed by passive recovery. Males completed an additional session of testing with single leg PECO. The mean arterial pressure during PECO and control was greater in males compared to females (p=0.004). The was a significant time by condition by sex interaction in the heart rate response to PECO (p=0.027). There was also a significant condition by sex interaction in the ventilatory response to PECO (p=0.026). In males, we observed a dose-dependent cardiovascular, but not ventilatory, response to muscle mass occluded (all p<0.05). Our findings suggest the metaboreflex contribution to cardiorespiratory control during dynamic exercise is greater in males compared to females. The ventilatory response induced by double-leg occlusion but not single-leg occlusion, suggests that the ventilatory influence of the metaboreflex is less sensitive than the cardiovascular response and may be linked to the greater afferent activation induced by double-leg occlusion.

The effects of biological sex and oral contraception on the sympathetic neurocirculatory adjustments to static handgrip exercise in humans.

Biological sex affects the neurocirculatory adjustments to fatiguing exercise. However, the effects of sex and oral contraceptive pills (OCPs) on sympathetic action potential (AP) emission patterns and the transduction of AP discharge into vasoconstriction during static handgrip (SHG) exercise remains unknown. We tested the hypothesis that males, and females using OCPs, would demonstrate larger increases in sympathetic activation and sympathetic vascular transduction compared to naturally menstruating females during SHG and post-exercise circulatory occlusion (PECO). Young males (n=14, 25[5] yr), females using OCPs (n=16, 24[6] yr), and naturally menstruating females (n=18, 26[4] yr) underwent assessments of multi-unit muscle sympathetic nerve activity (MSNA)/AP discharge patterns (microneurography), and femoral artery blood flow (ultrasound) during fatiguing SHG at 40% maximum voluntary contraction and 2-min PECO. Sympathetic vascular transduction was determined as the quotient of the change in leg vascular conductance (LVC) and MSNA/AP discharge. Males demonstrated greater increases in APs/burst (P=0.028) and total AP clusters (P=0.008) compared to naturally menstruating females only, but not those using OCPs during exercise. Sympathetic vascular transduction of MSNA burst amplitude, APs/burst, and total AP clusters was greater in males and females using OCPs compared to naturally menstruating females (range: P=0.004-0.044). In contrast, no group differences in AP discharge were observed during PECO (range: P=0.510-0.872), and AP discharge was not related to LVC during PECO (range: P=0.08-0.949). These data indicate that biological sex and OCP use impact the central generation of efferent AP discharge, as well as the transduction of these neuronal messages into peripheral vasoconstriction during static exercise.

Cardiovascular reflex contributions to sympathetic inhibition during low intensity dynamic leg exercise in healthy middle-age.

Aging augments resting muscle sympathetic nerve activity (MSNA) and sympatho-inhibition during mild dynamic 1-leg exercise. To elucidate which reflexes elicit exercise-induced inhibition, we recruited 19 (9 men) healthy volunteers (mean age 56 ± 9 SD years), assessed their peak oxygen uptake (VO2peak ), and, on another day, measured heart rate (HR), blood pressure (BP) and MSNA (microneurography) at rest and during 1-leg cycling (2 min each at 0 load and 30%-40% VO2peak ), 3 times: (1) seated +2 min of postexercise circulatory occlusion (PECO) (elicit muscle metaboreflex); (2) supine (stimulate cardiopulmonary baroreflexes);and (3) seated, breathing 32% oxygen (suppress peripheral chemoreceptor reflex). While seated, MSNA decreased similarly during mild and moderate exercise (p < 0.001) with no increase during PECO (p = 0.44). Supine posture lowered resting MSNA (main effect p = 0.01) BP and HR. MSNA fell further (p = 0.04) along with diastolic BP and HR during mild, not moderate, supine cycling. Hyperoxia attenuated resting (main effect p = 0.01), but not exercise MSNA. In healthy middle-age, the cardiopulmonary baroreflex and arterial chemoreflex modulate resting MSNA, but contrary to previous observations in young subjects, without counter-regulatory offset by the sympatho-excitatory metaboreflex, resulting in an augmented sympatho-inhibitory response to mild dynamic leg exercise.

Hemodynamic responses to handgrip and metaboreflex activation are exaggerated in individuals with metabolic syndrome independent of resting blood pressure, waist circumference, and fasting blood glucose.

Introduction: Prior studies report conflicting evidence regarding exercise pressor and metaboreflex responses in individuals with metabolic syndrome (MetS). Purpose: To test the hypotheses that 1) exercise pressor and metaboreflex responses are exaggerated in MetS and 2) these differences may be explained by elevated resting blood pressure. Methods: Blood pressure and heart rate (HR) were evaluated in 26 participants (13 MetS) during 2min of handgrip exercise followed by 3min of post-exercise circulatory occlusion (PECO). Systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP), along with HR and a cumulative blood pressure index (BPI), were compared between groups using independent samples t-tests, and analyses of covariance were used to adjust for differences in resting blood pressure, fasting blood glucose (FBG), and waist circumference (WC). Results: ΔSBP (∼78% and ∼54%), ΔMAP (∼67% and ∼55%), and BPI (∼16% and ∼20%) responses were significantly exaggerated in individuals with MetS during handgrip and PECO, respectively (all p ≤ 0.04). ΔDBP, ΔMAP, and BPI responses during handgrip remained significantly different between groups after independently covarying for resting blood pressure (p < 0.01), and after simultaneously covarying for resting blood pressure, FBG, and WC (p ≤ 0.03). Likewise, peak SBP, DBP, MAP, and BPI responses during PECO remained significantly different between groups after adjusting for resting blood pressure (p ≤ 0.03), with peak SBP, MAP, and BPI response remaining different between groups after adjusting for all three covariates simultaneously (p ≤ 0.04). Conclusion: These data suggest that exercise pressor and metaboreflex responses are significantly exaggerated in MetS independent of differences in resting blood pressure, FBG, or WC.

Effects of exercise induced muscle damage on cardiovascular responses to isometric muscle contractions and post-exercise circulatory occlusion

PurposeThe aim of the present study was to investigate whether exercise-induced muscle damage (EIMD) influences cardiovascular responses to isometric exercise and post-exercise circulatory occlusion (PECO). We hypothesized that EIMD would increase muscle afferent sensitivity and, accordingly, increase blood pressure responses to exercise and PECO.MethodsEleven male and nine female participants performed unilateral isometric knee extension at 30% of maximal voluntary contraction (MVC) for 3-min. A thigh cuff was rapidly inflated to 250 mmHg for two min PECO, followed by 3 min recovery. Heart rate and blood pressure were monitored beat-by-beat, with stroke volume and cardiac output estimated from the Modelflow algorithm. Measurements were taken before and 48 h after completing eccentric knee-extension contractions to induce muscle damage (EIMD).ResultsEIMD caused 21% decrease in MVC (baseline: 634.6 ± 229.3 N, 48 h: 504.0 ± 160 N), and a 17-fold increase in perceived soreness using a visual-analogue scale (0–100 mm; VASSQ) (both p < 0.001). CV responses to exercise and PECO were not different between pre and post EIMD. However, mean arterial pressure (MAP) was higher during the recovery phase after EIMD (p < 0.05). Significant associations were found between increases in MAP during exercise and VASSQ, Rate of Perceived Exertion (RPE) and Pain after EIMD only (all p < 0.05).ConclusionThe MAP correlations with muscle soreness, RPE and Pain during contractions of damaged muscles suggests that higher afferent activity was associated with higher MAP responses to exercise.

Muscle metaboreflex control of left ventricular systolic function in heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) exhibits exaggerated sympathoexcitation and altered cardiac and vascular responses to muscle metaboreflex activation (MMA). However, left ventricular (LV) responses to MMA are not well studied in patients with HFrEF. The purpose of this study was to examine LV function during MMA using cardiac magnetic resonance imaging (MRI) in patients with HFrEF. Thirteen patients with HFrEF and 18 healthy age-matched controls underwent cardiac MRI during rest and MMA. MMA protocol included 6 min of isometric handgrip exercise followed by 6-min of brachial postexercise circulatory occlusion. LV stroke volume index (SVi), end-systolic volume index (ESVi), end-diastolic volume index (EDVi), and global longitudinal strain (GLS) were measured by two- and four-chamber cine images. Volumes were indexed to body surface area. Heart rate (via ECG) and brachial mean arterial pressure (MAP) were recorded. Cardiac output and total peripheral resistance (TPR) were calculated. SVi decreased during MMA in HFrEF (P = 0.037) but not in controls (P = 0.392). ESVi (P = 0.007) and heart rate (P < 0.001) increased during MMA in HFrEF but not controls (P ≥ 0.170). TPR (P = 0.021) and MAP (P < 0.001) increased during MMA in both groups. Cardiac output (P = 0.946), EDVi (P = 0.177), and GLS (P = 0.619) were maintained from rest to MMA in both groups. Despite similarly maintained cardiac output, LV strain, and increased TPR in HFrEF and control groups, SVi decreased, and heart rate increased during MMA in patients with HFrEF. These findings suggest an impaired contractility reserve in response to increased TPR during MMA in HFrEF.NEW & NOTEWORTHY Stroke volume decreases and end-systolic volume increases during muscle metaboreflex activation in patients with heart failure with reduced ejection fraction (HFrEF), suggesting impaired contractile reserve during muscle metaboreflex activation in patients with HFrEF. Total peripheral resistance increases similarly during muscle metaboreflex activation in patients with HFrEF compared to controls, indicating normal levels of peripheral vasoconstriction during muscle metaboreflex activation in patients with HFrEF.

Renal vascular conductance is unrelated to leg vascular conductance or muscle sympathetic nerve activity at rest and during stress in humans.

The sympathetic nervous system is important for cardiovascular regulation, particularly during acute stress. Efferent sympathetic outflow can be regulated in an organ-dependent manner, but whether renal and leg vasoconstriction are associated at rest or during sympathetic stressors is unknown. Therefore, we sought to determine the relationships between muscle sympathetic nerve activity (MSNA), leg vascular conductance (LVC), and renal vascular conductance (RVC) at rest and during common laboratory-based sympathoexcitatory stimuli in a cohort of young healthy adults. Beat-to-beat arterial pressure (photoplethysmography), MSNA (microneurography), superficial femoral artery blood flow, and renal artery blood velocity (Doppler ultrasound) were measured at rest and during static handgrip exercise (30% maximal voluntary contraction), postexercise circulatory occlusion (PECO), and cold stress (hand in 3.8 ± 1.3°C water) in 37 young healthy adults (16 females, 21 males). At rest, RVC was unrelated to LVC (r = -0.11, P = 0.55) or MSNA burst frequency (ρ = -0.22, P = 0.26). Static handgrip, PECO, and cold stress each induced an increase in mean arterial pressure and MSNA and a reduction in RVC (all P < 0.001). LVC was unaltered during stress (all P ≥ 0.16), with the exception of a reduction during the second minute of cold stress (P = 0.03). During stress, changes in RVC were not associated with changes in LVC (handgrip: r = -0.24, P = 0.21; PECO: ρ = -0.04, P = 0.82; cold stress: r = -0.17, P = 0.38) or MSNA (handgrip: ρ = -0.14, P = 0.48; PECO: r = 0.27, P = 0.15; cold stress: r = -0.27, P = 0.16). Furthermore, MSNA was not associated with LVC at rest or during stress (all P ≥ 0.12). The present findings highlight the differential control of regional sympathetic vasoconstriction at rest and during stress in young healthy humans.NEW & NOTEWORTHY The sympathetic nervous system plays a critical role in cardiovascular regulation at rest and during stress. We demonstrate that renal artery vascular conductance is unrelated to superficial femoral artery vascular conductance or muscle sympathetic nerve activity at rest or during laboratory-based sympathetic stressors in young healthy adults. These findings support the concept of differential control of peripheral sympathetic outflow at rest and during stress in humans.

The interactive effects of age and sex on the neuro-cardiovascular responses during fatiguing rhythmic handgrip exercise.

The impact of age on exercise pressor responses is equivocal, likely because of sex-specific neuro-cardiovascular changes with age. However, assessments of the interactive effects of age and sex on muscle sympathetic nerve activity (MSNA) responses to exercise are lacking. We tested the hypothesis that older females would exhibit exaggerated increases in blood pressure (BP) and MSNA discharge patterns during handgrip exercise compared with similarly aged males and young adults. Twenty-five young (25 (2) years; mean (SD)) males (YM; n=12) and females (YF; n=13) and 23 older (71 (5) years) males (OM; n=11) and females (OF; n=12) underwent assessments of BP, total peripheral resistance (TPR; Modelflow) and MSNA action potential (AP) discharge patterns (microneurography) during incremental rhythmic handgrip exercise and post-exercise circulatory occlusion (PECO). OM demonstrated larger ∆BP and ∆TPR from baseline than YM (both P < 0.001) despite smaller increases in ∆APs/burst (OM: 0.4 (3) vs. YM: 5 (3) spikes/burst, P < 0.001) and ∆AP clusters/burst (OM: 0.1 (1) vs. YM: 1.8 (1) clusters/burst, P < 0.001) during exercise. Testosterone was lower in OM than YM (P < 0.001) and was inversely related to ∆BP but positively related to ∆AP clusters/burst in males (both P=0.03). Conversely, YF and OF demonstrated similar ∆BP and ∆AP discharge during exercise (range: P=0.75-0.96). Age and sex did not impact haemodynamics or AP discharge during PECO (range: P=0.08-0.94). Altogether, age-related changes in neuro-cardiovascular reactivity exist in males but not females during fatiguing exercise and seem to be related to testosterone. This sex-specific impact of age underscores the importance of considering biological sex when assessing age-related changes in neuro-cardiovascular control during exercise. KEY POINTS: Older males have the largest increase in blood pressure despite having the smallest increases in sympathetic vasomotor outflow during rhythmic handgrip exercise. Young males demonstrate greater increases in sympathetic action potential (AP) discharge compared with young females during rhythmic handgrip exercise. Older adults (regardless of sex) demonstrate smaller increases in muscle sympathetic nerve activity (MSNA) burst amplitude and total AP clusters compared with young adults during exercise, as well as smaller increases in integrated MSNA burst frequency, incidence and total MSNA activity during post-exercise circulatory occlusion (i.e. independent effect of age). Males, but not females (regardless of age), reflexively modify AP conduction velocity during exercise. Our results indicate that age and sex independently and interactively impact the neural and cardiovascular homeostatic adjustments to fatiguing small muscle mass exercise.

Sex-specific impact of aging on muscle sympathetic neural discharge patterns during incremental rhythmic handgrip exercise

Sex-disparities exist in the risk of developing hypertension throughout the lifespan, with a greater prevalence of hypertension amongst postmenopausal females compared to similarly aged males. Though the underlying mechanisms are multifactorial, exaggerated sympathetic neuro-cardiovascular reactivity may be an important contributor. Indeed, postmenopausal females exhibit exaggerated exercise pressor responses compared to young adults, and older males. However, the interactive effects of age and sex on muscle sympathetic nerve activity (MSNA) and action potential (AP) coding patterns during exercise remains unclear. We hypothesized that older females would exhibit the greatest increase in MSNA and AP recruitment during exercise and post-exercise circulatory occlusion (PECO) relative to young males and females, as well as older males. MSNA and AP discharge patterns (microneurography and continuous wavelet transform) were assessed in 12 young males (YM (mean±SD); 26±4, years), 11 young females (YF; 25±4 years), 11 older males (OM; 71±11 years), and 12 older females (OF; 71±4 years) during incremental rhythmic handgrip exercise to fatigue followed by 2 minutes of PECO. At peak exercise, OM demonstrated a smaller change from baseline (Δ) in MSNA burst incidence (BI) compared to all other groups (YM: Δ8±9, YF: Δ9±8, OM: Δ-6±8, OF: Δ6±7 bursts/100heartbeats; all ANOVA post-hoc P&lt;0.05), whereas ΔMSNA burst frequency (BF), Δburst amplitude (BA), and Δtotal activity were not different between groups (all P&gt;0.05). Conversely, YM demonstrated greater ΔAPs/burst (YM: Δ5±3, OM: Δ0.4±3, OF: Δ2±2 APs/burst; post-hoc P&lt;0.05) and ΔAP clusters/burst (YM: Δ2±1, OM: Δ0.1±1, OF: Δ0.7±0.7 Clusters/burst; post-hoc P&lt;0.05) compared to OM and OF, but not compared to YF (Δ2±3 APs/burst and Δ0.9±0.8 clusters/burst; both P≥0.07). However, no group differences were observed in the recruitment of larger axons (YM: Δ6±2, YF: Δ4±2, OM: Δ2±5, OF: Δ4±3 clusters; P=0.33). Contrary to exercise, group-by-time interactions existed during PECO for ΔMSNA BF ( P&lt;0.01), ΔBI ( P&lt;0.01), and Δtotal activity ( P&lt;0.01) where greater increases occurred during the first minute of PECO in young compared to older adults (all post-hoc P&lt;0.05), whereas in the final minute of PECO, MSNA ΔBF and ΔBI were only greater in YM compared to OM and OF (all P&lt;0.05), and total activity was greater in YM and YF compared to OF only (all P&lt;0.05). No group-by-time interactions were observed for ΔMSNA BA ( P=0.37), ΔAPs/burst ( P=0.94), ΔAP clusters/burst ( P=0.95) or Δtotal AP clusters ( P=0.41) during PECO. Altogether, MSNA and AP reactivity during exercise was not exaggerated in OF, but age-related reductions in AP recruitment were observed in males. During PECO, MSNA responses were lower in older relative to young adults but, AP recruitment was unaltered by age. Thus, exaggerated MSNA or AP reactivity may not explain the greater prevalence of hypertension in OF. Supported by the Natural Sciences and Engineering Council of Canada, and IEEM Indirect Funds. This is the full abstract presented at the American Physiology Summit 2023 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.

Sex Differences in Heart Rate Variability during Metaboreflex Activation

Women have been shown to experience blunted metaboreflex activation compared to men (Jarvis et al., 2011; Joshi &amp; Edgell, 2019; Minahan et al., 2018; Samora et al., 2020), which may derive from altered autonomic balance. Since heart rate variability (HRV) estimates sympathetic and parasympathetic outflow, this study aims to determine if there are sex differences in HRV during metaboreflex activation. High frequency (HF) power and greater RR interval variability (SDRR) represent cardiac parasympathetic outflow, whereas the ratio between low frequency (LF) and HF power (LF/HF) represents cardiac sympathetic outflow. Thirty-two young, healthy men (n=16) and women (n=16) were recruited to perform 2mins of isometric handgrip at 40% of their maximal voluntary contraction followed by 3mins of post-exercise circulatory occlusion (PECO). ECG was continuously recorded, and HRV analysis was determined using 3mins of ECG at baseline or PECO. In response to PECO, heart rate (Women 71±12bpm vs. 73±13bpm; Men 68±12bpm vs. 72±13bpm; p=0.026) and mean arterial pressure (Women 84±8mmHg vs. 93±10mmHg; Men 85±9mmHg vs. 97±11mmHg; p&lt;0.001) increased equally in both sexes. There were no significant differences in SDRR, root mean square standard deviation, and total power due to sex or PECO (all p&gt;0.07). At all timepoints and compared to men, women had 1) significantly lower LF power (Women 19±10nu vs. 24±16nu; Men 42±21nu vs. 49±17nu; p&lt;0.001), 2) higher HF power (Women 78±9nu vs. 74±16nu; Men 57±20nu vs. 50±17nu; p&lt;0.001), 3) higher proportion of RR intervals differences greater than 50ms (Women 60±21% vs. 58±22%; Men 39±16% vs. 35±20%; p=0.003), regardless of time (p&gt;0.2), and 4) lower LF/HF (Women 0.26±0.17 vs. 0.41±0.42; Men 1.01±0.90 vs. 1.34±1.30; p=0.002). Unlike previous findings, no sex differences were observed in the pressor response to metaboreflex activation. HRV did not differ in response to PECO in both sexes; however, women had greater cardiac parasympathetic dominance than men. Funding provided by Natural Sciences and Engineering Research Council of Canada This is the full abstract presented at the American Physiology Summit 2023 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.

Acute beetroot juice reduces blood pressure in young Black and White males but not females

A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3−)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3−) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3− were associated with reduced brachial systolic BP (ρ = −0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.

Ventilatory response to peripheral chemoreflex and muscle metaboreflex during static handgrip in healthy humans: evidence of hyperadditive integration.

What is the central question of this study? What is the effect of peripheral chemoreflex and muscle metaboreflex integration on ventilation regulation, and what is the effect of integration on breathing-related sensations and emotions? What is the main finding and its importance? Peripheral chemoreflex and muscle metaboreflex coactivation during isocapnic static handgrip exercise appeared to elicit a hyperadditive effect with regard to ventilation and an additive effect with regard to breathing-related sensations and emotions. These findings reveal the nature of the integration between two neural mechanisms that operate during small-muscle static exercise performed under hypoxia. Exercise augments the hypoxia-induced ventilatory response in an exercise intensity-dependent manner. A mutual influence of hypoxia-induced peripheral chemoreflex activation and exercise-induced muscle metaboreflex activation might mediate the augmentation phenomenon. However, the nature of these reflexes' integration (i.e., hyperadditive, additive or hypoadditive) remains unclear, and the coactivation effect on breathing-related sensations and emotions has not been explored. Accordingly, we investigated the effect of peripheral chemoreflex and muscle metaboreflex coactivation on ventilatory variables and breathing-related sensations and emotions during exercise. Fourteen healthy adults performed 2-min isocapnic static handgrip, first with the non-dominant hand and immediately after with the dominant hand. During the dominant hand exercise, we (a) did not manipulate either reflex (control); (b) activated the peripheral chemoreflex by hypoxia; (c) activated the muscle metaboreflex in the non-dominant arm by post-exercise circulatory occlusion (PECO); or (d) coactivated both reflexes by simultaneous hypoxia and PECO use. Ventilation response to coactivation of reflexes (mean±SD, 13±6l/min) was greater than the sum of responses to separated activations of reflexes (mean±SD, 8±8l/min, P=0.005). Breathing-related sensory and emotional responses were similar between coactivation of reflexes and the sum of separate activations of reflexes. Thus, the peripheral chemoreflex and muscle metaboreflex integration during exercise appeared to be hyperadditive with regard to ventilation and additive with regard to breathing-related sensations and emotions in healthy adults.

Blood Pressure Responses to Postexercise Circulatory Occlusion Are Attenuated After Exercise-Induced Muscle Weakness.

Exercise blood pressure (BP) responses are thought to be determined by relative exercise intensity (percent maximal voluntary contraction (MVC) strength). However, cross-sectional studies report that during a static contraction, higher absolute force is associated with greater BP responses to relative intensity exercise and subsequent muscle metaboreflex activation with postexercise circulatory occlusion (PECO). We hypothesized that a bout of unaccustomed eccentric exercise would reduce knee extensor MVC and subsequently attenuate BP responses to PECO. Continuous BP, heart rate, muscle oxygenation, and knee extensor electromyography were recorded in 21 young healthy individuals (female, n = 10) during 2 min of 20% MVC static knee extension exercise and 2 min of PECO, performed before and 24 h after 300 maximal knee extensor eccentric contractions to cause exercise-induced muscle weakness. As a control, 14 participants repeated the eccentric exercise 4 wks later to test whether BP responses were altered when exercise-induced muscle weakness was attenuated via the protective effects of the repeated bout effect. Eccentric exercise reduced MVC in all participants (144 ± 43 vs 110 ± 34 N·m, P < 0.0001). BP responses to matched relative intensity static exercise (lower absolute force) were unchanged after eccentric exercise ( P > 0.99) but were attenuated during PECO (systolic BP: 18 ± 10 vs 12 ± 9 mm Hg, P = 0.02). Exercise-induced muscle weakness modulated the deoxygenated hemoglobin response to static exercise (64% ± 22% vs 46% ± 22%, P = 0.04). When repeated after 4 wks, exercise-induced weakness after eccentric exercise was attenuated (-21.6% ± 14.3% vs -9.3 ± 9.7, P = 0.0002) and BP responses to PECO were not different from control values (all, P > 0.96). BP responses to muscle metaboreflex activation, but not exercise, are attenuated by exercise-induced muscle weakness, indicating a contribution of absolute exercise intensity on muscle metaboreflex activation.