Post-exercise Circulatory Occlusion Research Articles

Baroreflex resetting of human sympathetic action potential subpopulations during exercise.

This study tested the hypothesis that during fatiguing volitional exercise in humans, descending cortical signals and ascending skeletal muscle metaboreflex signals exert divergent control over baroreflex resetting of sympathetic action potential (AP) discharge. We quantified the baroreflex gain for sympathetic AP clusters within the muscle sympathetic nerve activity neurogram (peroneal microneurography and continuous wavelet transform) during baseline (BSL), the first 2-minutes of a 5-minute isometric handgrip (20% of maximal effort; IHG1), the last 2-minutes of IHG (IHG2), and during post-exercise circulatory occlusion (PECO) in seven healthy participants. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability (%) versus diastolic blood pressure (DBP; mmHg) for 10 normalized AP clusters. Compared to BSL, during IHG1, AP baroreflex threshold functions were only reset to greater DBP and baroreflex gain was unaffected. Compared to BSL, during IHG2 and PECO, baroreflex functions were reset to greater DBP and to greater AP firing probabilities, with medium-sized APs demonstrating the largest upward resetting (e.g., cluster 3 BSL: 26±7%, cluster 3 IHG2: 78±22%, cluster 3 PECO: 88±46%). Compared to BSL, AP baroreflex threshold gain was not different during IHG2 but was increased during PECO, with medium-sized APs demonstrating the largest increase in baroreflex gain (e.g., cluster 3 BSL: -6.31±3.1 %/mmHg, cluster 3 IHG2: ‑6.18±5.4 %/mmHg, cluster 3 PECO: ‑12.13±6.5 %/mmHg). These findings indicate that during IHG exercise, descending cortical signaling and ascending skeletal muscle metaboreceptor signals differentially affect baroreflex resetting of subpopulations of human muscle sympathetic postganglionic neurons.

The influence of training status and parasympathetic blockade on the cardiac rate, rhythm and functional response to autonomic stress.

Apnea (breath-holding) elicits co-activation of sympathetic and parasympathetic nervous systems, affecting cardiac control. In situations of autonomic co-activation (e.g., cold water immersion), cardiac arrhythmias are observed during apnea. Chronic endurance training reduces resting heart rate in part via elevation in parasympathetic tone, and has been identified as a risk factor for development of arrhythmias. However, few studies have investigated autonomic control of the heart in trained athletes during stress. Therefore, we determined whether heightened vagal tone resulting from endurance training promotes a higher incidence of arrhythmia during apnea. We assessed the heart rate, rhythm (ECG lead II), and cardiac inotropic (speckle-tracking echocardiography) response to apnea in 10 endurance trained and 7 untrained participants. Participants performed an apnea at rest and following sympathetic activation using post-exercise circulatory occlusion (PECO). All apneas were performed prior to (CON) and following vagal block using glycopyrrolate (GLY). Trained participants had lower heart rates at rest (p=0.03) and during apneas (p=0.009) under CON. At rest, 3 trained participants exhibited instances of junctional rhythm and 4 trained participants developed ectopy during CON apneas, whereas 3 untrained participants developed ectopic beats only with concurrent sympathetic activation (PECO). Following GLY, no arrhythmias were noted in either group. Vagal block also revealed increased cardiac chronotropy (heart rate) and inotropy (strain rate) during apnea, demonstrating a greater sympathetic influence in the absence of parasympathetic drive. Our results highlight that endurance athletes may be more susceptible to ectopy via elevated vagal tone, whereas untrained participants may only develop ectopy through autonomic conflict. .

Upper and lower limb muscle sympathetic responses to contralateral exercise in healthy humans: A pilot study.

Muscle sympathetic nerve activity (MSNA) is similar between limbs at rest, although a subset of MSNA bursts do demonstrate limb-specific discharge. Whether limb differences in MSNA synchronicity are present during exercise remains controversial. We concurrently measured MSNA from the radial and fibular nerves at rest and during rhythmic handgrip (RHG), static handgrip (SHG), and post-exercise circulatory occlusion (PECO). MSNA burst frequency and incidence were similar between nerve sites during all conditions. Synchronous bursts resulted in larger increases in sympathetic-blood pressure transduction compared to isolated bursts (∆+3.6±2.1 vs. +2.3±2.4mmHg, P=0.01). The proportion of bursts firing synchronously between nerves at rest was slightly increased during RHG ([rest vs. exercise; mean±SD] 45.3±7.1 vs. 61.6±7.2%) and similar during SHG (56.2±7.2 vs. 54±10.6%). In contrast, burst firing synchronicity increased during PECO (83.8±12.4%) alongside larger burst amplitudes. Inter-limb differences in resting MSNA are preserved during handgrip exercise, whereas isolated metaboreflex activation results in greater burst synchronization between limbs.

Habituation attenuates the sex-specific associations between ischemic pain, blood pressure, and arterial stiffness in young adults.

Cardiovascular reactivity (CVR) during physical stress is prognostic for incident cardiovascular disease. CVR is influenced by perceived pain. However, there is limited data on the effect of sex differences and repeated exposures to painful stimuli on CVR. We measured blood pressure (BP) and carotid-femoral pulse wave velocity (cf-PWV; an index of arterial stiffness) at rest, during isometric handgrip (HG) exercise at 30% of maximum voluntary contraction, and during postexercise circulatory occlusion (PECO) during two identical trials in 39 adults (20M/19F; 18-39 yr). We assessed participants' perceived pain using a visual analog scale after the first minute of each stimulus. We collected BP during minute 2 of each stimulus and cf-PWV during minute 3 of each stimulus. In male participants, we observed moderate associations (Ps ≤ 0.023) between perceived pain and changes in brachial diastolic (ρ = 0.620) and mean BP (ρ = 0.597); central diastolic, mean, and systolic BP (ρs = 0.519-0.654); and cf-PWV (ρ = 0.680) during PECO in trial 1, but not trial 2 (Ps ≥ 0.162). However, in female participants, there were no associations between pain and CVR indices during either trial (Ps ≥ 0.137). Irrespective of sex, reductions in perceived pain during trial 2 relative to trial 1 were weakly to moderately associated (Ps ≤ 0.038) with reductions in brachial diastolic (ρ = 0.346), mean (ρ = 0.379), and systolic BP (ρ = 0.333); central mean (ρ = 0.400) and systolic BP (ρ = 0.369); and cf-PWV (ρ = 0.526). These findings suggest that 1) there are sex differences in pain modulation of CVR in young adults and 2) habituation blunts pain and CVR during PECO, irrespective of sex.NEW & NOTEWORTHY We demonstrate sex differences in the association between pain perception and cardiovascular reactivity (CVR) during ischemic pain. We also demonstrate habituation to pain and reduced CVR during repeated exposure in a sex-independent manner. Accounting for sex differences and habituation may improve the prognostic utility of CVR.

Impaired Sympathetic Neural Recruitment During Skeletal Muscle Metaboreflex Activation in Women with Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that is more prevalent in women than men and has been linked to an elevated risk of developing cardiovascular disease. Although the physiological mechanisms are unclear, it is thought that exaggerated neuro‐cardiovascular reactivity is partially responsible. Indeed, women with PTSD demonstrate exaggerated muscle sympathetic nerve activity (MSNA) responses at the onset of exercise. However, it is unknown whether PTSD modifies the underlying sympathetic action potentials (AP) coding patterns that comprise the integrated MSNA signal during fatiguing exercise in women. We therefore hypothesized that women with PTSD will exhibit exaggerated MSNA and AP recruitment compared to women without PTSD during fatiguing handgrip exercise. MSNA and AP discharge patterns (via microneurography and a continuous wavelet transform) were assessed in eleven women with PTSD (43±11 [SD] years) and thirteen women without PTSD (Controls; 40±8 years) during isometric handgrip exercise (IHG) to fatigue at 40% of maximal voluntary contraction (MVC) force, followed by 2 minutes of post‐exercise circulatory occlusion (PECO), and three minutes of recovery. The IHG time was divided equally into five stages. IHG duration (P=0.867) and MVC (P=0.226) were similar between both groups. PTSD did not modify the increase in MSNA and AP frequency or incidence during IHG and PECO (all group‐by‐stage interactions: P=0.294‐0.380). Conversely, throughout IHG and PECO, AP content per burst was greater in the Controls compared to women with PTSD (main effect of group: P=0.026). Furthermore, relative to Controls, women with PTSD were unable to increase the number of AP clusters per burst during the first (Controls: ∆1.3±1.2 vs. PTSD: ∆‐0.2±0.8 clusters/burst; P=0.016) and last minute (Controls: ∆1.2±1.1 vs. PTSD: ∆‐0.1±0.8 clusters/burst; P=0.022) of PECO, and recruited fewer subpopulations of previously silent axons during the first (Controls: ∆5±4 vs. PTSD: ∆1±2 clusters; P=0.020) and last minute (Controls: ∆4±2 vs. PTSD: ∆1±2 clusters; P=0.021) of PECO. Lastly, although an interaction effect was observed for the AP cluster size‐latency relationship during IHG and PECO (P=0.042), post‐hoc analyses revealed that PTSD did not modify this relationship (all P=0.658‐0.999). These data indicate that the central features of sympathetic outflow are impaired in women with PTSD during skeletal muscle metaboreflex activation.

Sympathetic Responses to Isometric Handgrip Exercise in Women following Preeclamptic Pregnancies

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

Acute changes in forearm vascular compliance during transient sympatho-excitation.

The study of vascular regulation often omits important information about the elastic properties of arteries under conditions of pulsatile flow. The purpose of this study was to examine the relationship between muscle sympathetic nerve activity (MSNA), vascular bed compliance, and peripheral blood flow responses in humans. We hypothesized that increases in MSNA would correlate with reductions in vascular compliance, and that changes in compliance would correspond with changes in peripheral blood flow during sympatho‐excitation. MSNA (microneurography), blood pressure (Finopres), and brachial artery blood flow (Doppler ultrasound), were monitored in six healthy males at baseline and during the last 15 s of voluntary end‐inspiratory, expiratory apneas and 5 min of static handgrip exercise (SHG; 20% maximum voluntary contraction) and 3 min of post‐exercise circulatory occlusion (SHG + PECO; measured in the non‐exercising arm). A lumped Windkessel model was employed to examine vascular bed compliance. During apnea, indices of MSNA were inversely related with vascular compliance, and reductions in compliance correlated with decreased brachial blood flow rate. During SHG, despite increased MSNA, compliance also increased, but was unrelated to increases in blood flow. Neither during SHG nor PECO did indices of MSNA correlate with forearm vascular compliance nor did vascular compliance correlate with brachial flow. However, during PECO, a linear combination of blood pressure and total MSNA was correlated with vascular compliance. These data indicate the elastic components of the forearm vasculature are regulated by adrenergic and myogenic mechanisms during sympatho‐excitation, but in a reflex‐dependent manner.

Cardiorespiratory responses to muscle metaboreflex activation in fibrosing interstitial lung disease.

New Findings What is the central question of this study? We determined whether sensory feedback from metabolically sensitive skeletal muscle afferents (metaboreflex) causes a greater ventilatory response and higher dyspnoea ratings in fibrosing interstitial lung disease (FILD). What is the main finding and its importance? Ventilatory responses and dyspnoea ratings during handgrip exercise and metaboreflex isolation were not different in FILD and control groups. Blood pressure and heart rate responses to handgrip were attenuated in FILD but not different to controls during metaboreflex isolation. These findings suggest that the muscle metaboreflex contribution to the respiratory response to exercise is not altered in FILD. Exercise limitation and dyspnoea are hallmarks of fibrosing interstitial lung disease (FILD); however, the physiological mechanisms are poorly understood. In other respiratory diseases, there is evidence that an augmented muscle metaboreflex may be implicated. We hypothesized that metaboreflex activation in FILD would result in elevated ventilation and dyspnoea ratings compared to healthy controls, due to augmented muscle metaboreflex. Sixteen FILD patients (three women, 69±14 years; mean±SD) and 16 age‐matched controls (four women, 67±7 years) were recruited. In a randomized cross‐over design, participants completed two min of rhythmic handgrip followed by either (i) two min of post‐exercise circulatory occlusion (PECO trial) to isolate muscle metaboreflex activation, or (ii) rested for four min (Control trial). Minute ventilation (V˙E; pneumotachometer), dyspnoea ratings (0–10 Borg scale), mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR; electrocardiogram) were measured. V˙E was higher in the FILD group at baseline and exercise increased V˙E similarly in both groups. V˙E remained elevated during PECO, but there was no between‐group difference in the magnitude of this response (ΔV˙E FILD 4.2 ± 2.5 L·min–1 vs. controls 3.6 ± 2.4 L·min–1, P = 0.596). At the end of PECO, dyspnoea ratings in FILD were similar to controls (1.0 ± 1.3 units vs. 0.5 ± 1.1 units). Exercise increased MAP and HR (P < 0.05) in both groups; however, responses were lower in FILD. Collectively, these findings suggest that there is not an augmented effect of the muscle metaboreflex on breathing and dyspnoea in FILD, but haemodynamic responses to handgrip are reduced relative to controls.

Impaired sympathetic neural recruitment during exercise pressor reflex activation in women with post-traumatic stress disorder.

Muscle sympathetic nerve activity (MSNA) increases during isometric exercise via increased firing of low-threshold action potentials (AP), recruitment of larger, higher-threshold APs, and synaptic delay modifications. Recent work found that women with post-traumatic stress disorder (PTSD) demonstrate exaggerated early-onset MSNA responses to exercise; however, it is unclear how PTSD affects AP recruitment patterns during fatiguing exercise. We hypothesized that women with PTSD (n = 11, 43[11] [SD] years) would exhibit exaggerated sympathetic neural recruitment compared to women without PTSD (controls; n = 13, 40[8] years). MSNA and AP discharge patterns (via microneurography and a continuous wavelet transform) were measured during 1 min of baseline, isometric handgrip exercise (IHG) to fatigue, 2 min of post-exercise circulatory occlusion (PECO), and 3 min of recovery. Women with PTSD were unable to increase AP content per burst compared to controls throughout IHG and PECO (main effect of group: P = 0.026). Furthermore, relative to controls, women with PTSD recruited fewer AP clusters per burst during the first (controls: ∆1.3[1.2] vs. PTSD: ∆-0.2[0.8]; P = 0.016) and second minute (controls: ∆1.2[1.1] vs. PTSD: ∆-0.1[0.8]; P = 0.022) of PECO, and fewer subpopulations of larger, previously silent axons during the first (controls: ∆5[4] vs. PTSD: ∆1[2]; P = 0.020) and second minute (controls: ∆4[2] vs. PTSD: ∆1[2]; P = 0.021) of PECO. Conversely, PTSD did not modify the AP cluster size-latency relationship during baseline, the end of IHG, or PECO (all P = 0.658-0.745). Collectively, these data indicate that women with PTSD demonstrate inherent impairments in the fundamental neural coding patterns elicited by the sympathetic nervous system during IHG and exercise pressor reflex activation.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Sex differences in the coronary vascular response to combined chemoreflex and metaboreflex stimulation in healthy humans.

What is the central question of this study? Coronary blood flow in healthy humans is controlled by both local metabolic signalling and adrenergic activity: does the integration of these signals during acute hypoxia and adrenergic activation differ between sexes? What are the main findings and its importance? Both males and females exhibit an increase in coronary blood velocity in response to acute hypoxia, a response that is constrained by adrenergic stimulation in males but not females. These findings suggest that coronary blood flow control differs between males and females. Coronary hyperaemia is mediated through multiple signalling pathways, including local metabolic messengers and adrenergic stimulation. This study aimed to determine whether the coronary vascular response to adrenergic stressors is different between sexes in normoxia and hypoxia. Young, healthy participants (n=32; 16F) underwent three randomized trials of isometric handgrip exercise followed by post-exercise circulatory occlusion (PECO) to activate the muscle metaboreflex. End-tidal was controlled at (1) normoxic levels throughout the trial, (2) 50mmHg for the duration of the trial (hypoxia trial), or (3) 50mmHg only during PECO (mixed trial). Mean left anterior descending coronary artery velocity (LADVmean ; transthoracic Doppler echocardiography), heart rate and blood pressure were assessed at baseline and during PECO. In normoxia, there was no change in LADVmean or cardiac workload induced by PECO in males and females. Acute hypoxia increased baseline LADVmean to a greater extent in males compared with females (P<0.05), despite a similar increase in cardiac workload. The change in LADVmean induced by PECO was similar between sexes in normoxia (P=0.31), greater in males during the mixed trial (male: 12.8 (7.7) cm/s vs. female: 8.1 (6.3) cm/s; P=0.02) and reduced in males but not females in acute hypoxia (male: -4.8 (4.5) cm/s vs. female: 0.8 (6.2) cm/s; P=0.006). In summary, sex differences in the coronary vasodilatory response to hypoxia were observed, and metaboreflex activation during hypoxia caused a paradoxical reduction in coronary blood velocity in males but not females.

Sex Differences in Muscle Metaboreflex Activation after Static Handgrip Exercise.

Larger blood pressure (BP) responses to relative-intensity static exercise in men versus women are thought to involve altered muscle metaboreflex activation, but whether this is because of an intrinsic sex difference in metabolite production or differences in muscle strength and absolute load is unknown. Continuous BP and heart rate were recorded in 200 healthy young men and women (women: n = 109) during 2 min of static handgrip exercise at 30% of maximal voluntary contraction (MVC), followed by 2 min of postexercise circulatory occlusion (PECO). Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (n = 39; women, n = 21), permitting calculation of signal-averaged resting sympathetic transduction (MSNA-diastolic BP). Sex differences were examined with and without statistical adjustment for MVC. Multivariate regression analyses were performed to identify predictors of BP responses. Men had larger systolic BP responses (interactions, P < 0.0001) to static handgrip exercise (24 ± 10 vs 17 ± 9 mm Hg [mean ± SD], P < 0.0001) and PECO (20 ± 11 vs 16 ± 9 mm Hg, P < 0.0001). Adjustment for MVC abolished these sex differences in BP (interactions, P > 0.7). In the subset with MSNA, neither burst frequency or incidence responses to static handgrip exercise or PECO differed between men and women (interactions, P > 0.2). Resting sympathetic transduction was also similar (P = 0.8). Multiple linear regression analysis showed that MVC or the change in MSNA, were predictors of BP responses to static handgrip, but only MVC was associated with BP responses during PECO. Sex differences in absolute contraction load contribute to differences in BP responses during muscle metaboreflex isolation using PECO. These data do not support an intrinsic effect of sex as being responsible for exercise BP differences between men and women.

Menstrual phase does not influence ventilatory responses to group III/IV afferent signaling in eumenorrheic young females

Estrogen can reduce sympathetic activity, but its effects on minute ventilation (VE) with group III/IV afferent activation remain unclear. This study examined the influence of estrogen on VE during lower-extremity exercise with group III/IV activation. Females completed two identical visits in follicular and ovulatory menstrual phases. Nine participants (age 25 ± 4 years) performed three minutes of baseline steady-state cycle ergometry and then group III/IV afferents were further activated with proximal thigh cuffs inflated to 20, 60, and 100 mmHg (randomized) for two minutes and five minutes of cycling between each occlusion. Metaboreflex was isolated by post-exercise circulatory occlusion. Ventilation was measured continuously and rating of perceived exertion (RPE) was recorded for each stage. During rest and exercise, VE (p < 0.001) and tidal volume (VT) (p = 0.033) were higher in the follicular than ovulatory phase. Minute ventilation, VT, and respiratory rate (RR) with ergoreflex and metaboreflex activation were similar across phases. With cuff occlusion of 100 mmHg, VE increased from baseline by 26.3 ± 7.0 L/min in the follicular phase (p < 0.001) and by 25.3±7.7 L/min in the ovulatory phase (p < 0.001), with no difference between phases (p> 0.05); RR and VT increased similarly with occlusion, also with no phase differences. In eumenorrheic females, menstrual phase influences ventilation but not ventilatory responses to group III/IV isolation.

Muscle Metaboreflex Control of Sympathetic Activity Is Preserved after Acute Intermittent Hypercapnic Hypoxia.

In normotensive patients with obstructive sleep apnea (OSA), the muscle sympathetic nerve activity (MSNA) response to exercise is increased while metaboreflex control of MSNA is decreased. We tested the hypotheses that acute intermittent hypercapnic hypoxia (IHH) in males free from OSA and associated comorbidities would augment the MSNA response to exercise but attenuate the change in MSNA during metaboreflex activation. Thirteen healthy males (age = 24 ± 4 yr) were exposed to 40 min of IHH. Before and after IHH, the pressor response to exercise was studied during 2 min of isometric handgrip exercise (at 30% maximal voluntary contraction), whereas the metaboreflex was studied during 4 min of postexercise circulatory occlusion (PECO). Mean arterial pressure (MAP), heart rate (HR), and fibular MSNA were recorded continuously. MSNA was quantified as burst frequency (BF) and total activity (TA). Mixed effects linear models were used to compare the exercise pressor and metaboreflex before and after IHH. As expected, IHH led to significant increases in MSNA BF, TA, and MAP at baseline and throughout exercise and PECO. However, during handgrip exercise, the change from baseline in MAP, HR, MSNA BF, and TA was similar before and after IHH (All P > 0.31). During PECO, the change from baseline in MSNA BF and TA was similar after IHH, whereas the change from baseline in MAP (Δ14 mm Hg, 95% CI = 7-19, vs Δ16 mm Hg, 95% CI = 10-21; P < 0.01) was modestly increased. After acute IHH, MSNA response to handgrip exercise and metaboreflex activation were preserved in healthy young males despite overall increases in resting MSNA and MAP. Chronic IHH and comorbidities often associated with OSA may be required to modulate the exercise pressor reflex and metaboreflex.

Sympathetic activation due to limb venous distension is preserved during muscle metaboreceptor stimulation

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans (venous distension reflex). It is unclear if the inputs from metabolically sensitive skeletal muscle afferents (i.e. muscle metaboreflex) would modify venous distension reflex. We hypothesized that muscle metaboreceptor stimulation might augment the venous distension reflex. BP (Finapres), heart rate (ECG), and MSNA (microneurography) were assessed in 18 young healthy subjects. In trial A, saline (5% forearm volume) was infused into the veins of an arterially occluded arm (non-handgrip trial). In trial B, subjects performed 2 min static handgrip followed by post exercise circulatory occlusion (PECO) of the arm. During PECO, saline was infused into veins of the arm (handgrip trial). In trial A, the infusion increased MSNA and BP as expected (both P < 0.001). In trial B, handgrip significantly raised MSNA, BP and venous lactic acid concentrations. Venous saline infusion during PECO further raised MSNA and BP (both P < 0.001). The changes in MSNA (D8.6 ± 1.5 to D10.6 ± 1.8 bursts/min, P = 0.258) and mean arterial pressure (P = 0.844) evoked by the infusion during PECO were not significantly different from those in the non-handgrip trial. These observations indicate that venous distension reflex responses are preserved during sympathetic activation mediated by the muscle metaboreflex.

Exercise Pressor Reflex is Attenuated during Moderate Whole‐Body Heating in Older Humans

Prior reports show that whole-body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole-body heating (WBH, e.g. increase in internal temperature Tcore ~0.4-0.5 °C) on sympathetic and cardiovascular responses to exercise in older healthy humans remains unclear. We examined muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP) and heart rate (HR) in 14 older (62 ± 7 yrs. mean ± SD) healthy subjects during fatiguing isometric handgrip exercise and post exercise circulatory occlusion (PECO). The protocol was performed under normothermic and moderate WBH conditions during 2 visits. Under the moderate WBH condition (ΔTcore ~0.4 ± 0.1 °C), MAP decreased (90.0 ± 6.6 to 86.4 ± 7.1 mmHg), HR increased (60.8 ± 7.9 to 71.7 ± 9.7 beats/min), while MSNA was unchanged (34.7 ± 9.2 to 37.5 ± 15.4 bursts/min) from the baseline before heating. Hemodynamic variables and MSNA did not change significantly during the time control period in the normothermic trial. Compared with the normothermic trial, the absolute MAP during fatiguing exercise (102.7 ± 8.5 vs. 117.2 ± 11.4 mmHg) and PECO (98.2 ± 8.9 vs. 113.9 ± 12.5 mmHg) were lower during the WBH trial. Moreover, MSNA (Δ8.4 ± 6.5 vs. Δ14.0 ± 7.2 bursts/min) and MAP (Δ16.5 ± 7.5 vs. Δ23.2 ± 8.2 mmHg) responses (i.e. changes) to fatiguing exercise were also less than those seen during the normothermic trial. These data suggest that moderate WBH attenuates reflex exercise pressor responses in older healthy humans. Further studies are needed to examine if WBH can attenuate exercise pressor responses in patients with cardiovascular diseases.

Moderate whole body heating attenuates the exercise pressor reflex responses in older humans.

Prior reports show that whole body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole body heating (WBH; e.g., increase in internal temperature Tcore of ∼0.4°C-0.5°C) or limb heating on sympathetic and cardiovascular responses to exercise in older healthy humans remain unclear. We examined the muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and heart rate (HR) in 14 older (62 ± 2 yr) healthy subjects during fatiguing isometric handgrip exercise and postexercise circulatory occlusion (PECO). The protocol was performed under normothermic, moderate WBH, and local limb (i.e., forearm) heating conditions during three visits. During the mild WBH stage (increase in Tcore of <0.3°C), HR increased, whereas BP and MSNA decreased from baseline. Under the moderate WBH condition (increase in Tcore of ∼0.4°C), BP decreased, HR increased, and MSNA was unchanged from baseline. Compared with the normothermic trial, the absolute MAP during fatiguing exercise and PECO was lower during the WBH trial. Moreover, MSNA and MAP responses (i.e., changes) to fatiguing exercise were also less than those seen during the normothermic trial. Limb heating induced a similar increase in forearm muscle temperature to that seen in the WBH trial (∼0.7°C-1.5°C). Limb heating did not alter resting MAP, HR, or MSNA. The MSNA and hemodynamic responses to exercise in the limb heating trial were not different from those in the normothermic trial. These data suggest that moderate WBH attenuates MSNA and BP responses to exercise in older healthy humans.

The sympathetic muscle metaboreflex is not different in the third trimester in normotensive pregnant women.

Isometric handgrip (IHG) is used to assess sympathetic nervous system responses to exercise and may be useful at predicting hypertension in both pregnant and nonpregnant populations. We previously observed altered sympathetic nervous system control of blood pressure in late pregnancy. Therefore, we measured muscle sympathetic nerve activity (MSNA) and blood pressure during muscle metaboreflex activation (IHG) in normotensive pregnant women in the third trimester compared with in healthy nonpregnant women. Further, 19 pregnant (32 ± 3 wk gestation) and 14 nonpregnant women were matched for age, non/prepregnant body mass index (BMI), and parity. MSNA (microneurography), heart rate (ECG), and arterial blood pressure (Finometer) were continuously recorded during 10 min of rest, and then during 2 min of IHG at 30% of maximal voluntary contraction, and 2 min of postexercise circulatory occlusion (PECO). Baseline sympathetic nerve activity (SNA) was elevated in pregnant (41 ± 11 bursts/min) compared with nonpregnant women (27 ± 9 bursts/min; P = 0.005); however, the sympathetic baroreflex gain and neurovascular transduction were not different between groups (P = 0.62 and P = 0.32, respectively). During IHG and PECO, there were no significant differences in the pressor responses (ΔMAP) between groups, (P = 0.25, main effect of group) nor was the sympathetic response different between groups (interaction effect: P = 0.16, 0.25, and 0.27 for burst frequency, burst incidence, and total SNA, respectively). These data suggest that pregnant women who have maintained sympathetic baroreflex and neurovascular transduction also have similar sympathetic and pressor responses during exercise.NEW & NOTEWORTHY We compared sympathetic nervous system activation by muscle metaboreflex between pregnant women in the third trimester and nonpregnant women. We show that the sympathetic nerve activity and associated pressor responses to isometric handgrip and post-exercise circulatory occlusion are not different between third-trimester pregnant and nonpregnant women. These data suggest that unlike other reflexes (e.g., cold pressor test or head-up tilt), metaboreflex control is maintained in pregnant women.

Oral contraceptives and menstrual cycle influence autonomic reflex function

Progesterone and its analogues are known to influence ventilation. Therefore, the purpose of this study was to investigate the role of endogenous and pharmaceutical female sex hormones in ventilatory control during the activation of the metaboreflex, mechanoreflex, and CO2 chemoreflex. Women aged 18–30 taking (n = 14) or not taking (n = 12) oral contraceptives (OC and NOC, respectively) were tested in the low hormone (LH) and high hormone (HH) conditions corresponding to the early follicular and mid‐luteal phases (NOC) or placebo and high‐dose pills (OC). Women underwent three randomized trials: (a) 3 min of passive leg movement (PLM), (b) 2 min of 40% maximal voluntary handgrip exercise followed by 2 min of post‐exercise circulatory occlusion (PECO), and (c) 5 min of breathing 5% CO2. We primarily measured hemodynamics and ventilation. During PLM, the OC group had a smaller pressor response (p = .012). During PECO, the OC group similarly exhibited a smaller pressor response (p = .043) and also exhibited a greater ventilatory response (p = .024). Lastly, in response to breathing 5% CO2, women in the HH phase had a greater ventilatory response (p = .022). We found that OC use attenuates the pressor response to both the metaboreflex and mechanoreflex while increasing the ventilatory response to metaboreflex activation. We also found evidence of an enhanced CO2 chemoreflex in the HH phase. We hypothesize that OC effects are from the chronic upregulation of pulmonary and vascular β‐adrenergic receptors. We further suggest that the increased cyclic progesterone in the HH phase enhances the chemoreflex.

Muscle Temperature During Exercise Under Whole-body Heating And Limb Heating Conditions

Prior studies suggest that moderate whole-body heating (WBH), which raises internal temperature (Tcore) ~0.6-1.0 deg C, alters the exercise pressor reflex. It is speculated that elevated muscle temperature (Tmuscle) alters the sensitivity of muscle afferents. However, less is known about the effects of passive WBH on the limb Tmuscle during exercise. PURPOSE: To determine limb Tmuscle during exercise under passive WBH and limb heating conditions. METHODS:Forearm Tmuscle was measured with a needle probe (thermocouple) in 8 healthy subjects (57 +- 3 yrs). Mean skin temperature (Tsk), Tcore (telemetric pill), the arm skin temperature (Tarmskin, not covered by suits), blood pressure (BP) and heart rate (HR) were measured during WBH with water perfused suits. After Tcore rose ~0.6 deg C, subjects performed a fatiguing handgrip exercise followed by post exercise circulatory occlusion (PECO). In a separate visit, the forearm was heated with a water perfused sleeve. After the Tmuscle rose ~1 deg C (i.e. similar to that seen during WBH), the exercise paradigm was repeated. RESULTS: Passive WBH significantly raised Tsk (3.2 +- 0.3 deg C), Tarmskin (1.9 +- 1.0 deg C), Tmuscle (0.96 +- 0.15 deg C) and HR. The increases in Tmuscle were positively correlated with the increases in Tcore (R = 0.75, P < 0.05). Limb heating raised Tmuscle (0.98 +- 0.11 deg C), Tarmskin (2.3 +- 0.6 deg C), and did not alter Tsk, Tcore or HR. There was no significant difference in the grip force, grip time, or the change in HR with handgrip between the trials. The increases in Tmuscle during the last min of grip (0.37 +- 0.07 vs. 0.92 +- 0.17 deg C, P < 0.03) and PECO (P = 0.01) were significantly lower during WBH than during the limb heating trial. CONCLUSION: Although local limb heating and WBH induced similar elevations in Tmuscle, the responses in Tmuscle to exercise were different between these two heating conditions. Supported by NIH R01 HL141198 (Li and Cui) and UL1 TR002014 (Sinoway), and AHA Award #15GRNT24480051 (Cui).