Sex differences in cardiac vagal reactivation from the end of isometric handgrip exercise and at the onset of muscle metaboreflex isolation.

A parasympathetic reactivation is an underlying mechanism mediating the rapid fall in heart rate (HR) at the onset of post-exercise ischemia (PEI) in humans. Herein, we tested the hypothesis that, compared to men, women present a slower HR recovery at the cessation of isometric handgrip exercise (i.e., onset of PEI) due to an attenuated cardiac vagal reactivation. Forty-seven (23 women) young and healthy volunteers were recruited. Subjects performed 90s of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 3-min of PEI. The onset of PEI was analyzed over the first 30s in 10s windows. Cardiac vagal reactivation was indexed using the HR fall and by HR variability metrics (e.g., RMSSD and SDNN) immediately after the cessation of the exercise. HR was significantly increased from rest during exercise in men and women and increases were similar between sexes. However, following the cessation of exercise, the HR recovery was significantly slower in women compared to men regardless of the time point (women vs. men: ∆-14 ± 8 vs. ∆-18 ± 6 beats.min-1 at 10s; ∆-20 ± 9 vs. ∆-25 ± 8 beats.min-1 at 20s; ∆-22 ± 10 vs. ∆-27 ± 9 beats.min-1 at 30s; P = .027). RMSSD and SDNN increased at the cessation of exercise in greater magnitude in men compared to women. These findings demonstrate that women had a slower HR recovery at the cessation of isometric handgrip exercise and onset of PEI compared to men, suggesting a sex-related difference in cardiac vagal reactivation in healthy young humans.

Sex differences in blood pressure regulation during ischemic isometric exercise: the role of the ß-adrenergic receptors.

We sought to investigate whether the ß-adrenergic receptors play a pivotal role in sex-related differences in arterial blood pressure (BP) regulation during isometric exercise. Sixteen volunteers (8 women) performed 2 min of ischemic isometric handgrip exercise (IHE) and 2 min of postexercise circulatory occlusion (PECO). Heart rate (HR) and beat-to-beat arterial BP were continuously measured. Beat-to-beat estimates of stroke volume (ModelFlow) were obtained and matched with HR to calculate cardiac output (Q̇) and total peripheral resistance (TPR). Two trials were randomly conducted between placebo and nonselective ß-adrenergic blockade (40 mg propranolol). Under the placebo condition, the magnitude of the BP response in IHE was lower in women compared with men. During PECO, the BP remained elevated and the sex differences persisted. The ß-blockade attenuated the BP response during IHE in men (∆57 ± 4 vs. ∆45 ± 7 mmHg, P = 0.025) due to a reduction in Q̇ (∆3.7 ± 0.5 vs. ∆1.8 ± 0.2 L/min, P = 0.012) while TPR was not affected. In women, however, the BP response during IHE was unchanged (∆27 ± 3 vs. ∆28 ± 3 mmHg, P = 0.889), despite attenuated Q̇ (∆2.7 ± 0.4 vs. ∆1.3 ± 0.2 L/min, P = 0.012). These responses were mediated by a robust increase in TPR under ß-blockade (∆-0.2 ± 0.4 vs. ∆2.2 ± 0.7 mmHg·L-1·min, P = 0.012). These findings demonstrate that the sex differences in arterial BP regulation during ischemic IHE are mediated by ß-adrenergic receptors.NEW & NOTEWORTHY We found that the blood pressure response during isometric exercise in women is mediated by increases in cardiac output, whereas in men it is mediated by increases in both cardiac output and total peripheral resistance. In addition, women showed a robust increase in total peripheral resistance under ß-blockade during isometric exercise and muscle metaboreflex activation. These findings demonstrate that sex differences in blood pressure regulation during isometric exercise are mediated by ß-adrenergic receptors.

Circulatory responses at the onset of handgrip exercise in patients with Parkinson's disease.

NEW FINDINGS: What is the central question of this study? The initial circulatory response to isometric exercise in young healthy subjects is thought to be cholinergically mediated. Do patients with Parkinson's disease, a specific population known to present cholinergic dysfunction, present impairment in these initial circulatory responses? What is the main finding and its importance? The initial reduction in total peripheral resistance was absent in patients with Parkinson's disease and in older subjects, which augmented the pressor response at the onset of isometric handgrip exercise. Given that cholinergic mechanisms play an important role in the circulatory responses at the onset of isometric exercise in humans, our data suggest that cholinergic mechanisms might be compromised with ageing. ABSTRACT: Physical exercise has been used as coping strategy for Parkinson's disease (PD). Thus, a better understanding of circulatory responses to exercise in this population is warranted. During the onset of isometric handgrip (IHG) exercise there is an increase in blood pressure (BP) and a reduction in the total peripheral resistance (TPR) in young subjects. This immediate reduction of TPR is thought to be mediated by a cholinergic mechanism. Given that PD also affects cholinergic neurons, we hypothesized that patients with PD would present blunted circulatory responses at the onset of IHG exercise. Mean BP, stroke volume, heart rate, cardiac output and TPR were measured during performance of 20 s of IHG at 40% maximal voluntary contraction in 12 patients with PD (66 ± 2 years old, 171 ± 7 cm, 74 ± 7 kg), 11 older subjects (65 ± 9 years old, 171 ± 7 cm, 74 ± 10 kg) and 10 young subjects (21 ± 1 years old, 178 ± 6 cm, 79 ± 9 kg). Isometric handgrip elicited an augmented BP increase in patients with PD and older subjects at 10 and 20 s compared with young subjects. However, the BP augmentation was lower at 20 s in patients with PD. The IHG-induced reduction in TPR was attenuated in patients with PD and older subjects compared with young subjects. Our results show that the circulatory responses at the onset of IHG are impaired in patients with PD and older subjects. Overall, these findings suggest that the cholinergic mechanism might be compromised with ageing.

Spontaneous cardiac baroreflex sensitivity is enhanced during post-exercise ischemia in men but not in women.

PURPOSE: To investigate the effect of isolated muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity (cBRS), and to characterize the potential sex-related differences in this interaction in young healthy subjects. METHODS: 40 volunteers (20 men and 20 women, age: 22 ± 0.4 year) were recruited. After 5-min rest period, the subjects performed 90 s of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 3 min of post-exercise ischemia (PEI). Beat-to-beat heart rate and arterial blood pressure were continuously measured by finger photopletysmography. Spontaneous cBRS was assessed using the sequence technique and heart rate variability was measured in time (RMSSD-standard deviation of the RR intervals) and frequency domains (LF-low and HF-high frequency power). RESULTS: Resting cBRS was similar between men and women. During PEI, cBRS was increased in men (Δ3.0 ± 1.1 ms mmHg- 1, P = 0.03) but was unchanged in women (Δ-0.04 ± 1.0 ms mmHg- 1, P = 0.97). In addition, RMSSD and HF power of heart rate variability increased in women (Δ7.4 ± 2.6 ms, P = 0.02; Δ373.4 ± 197.3 ms2; P = 0.04, respectively) and further increased in men (Δ26.4 ± 7.1 ms, P < 0.01; Δ1874.9 ± 756.2 ms2; P = 0.02, respectively). Arterial blood pressure increased from rest during handgrip exercise and remained elevated during PEI in both groups, however, these responses were attenuated in women. CONCLUSIONS: These findings allow us to suggest a sex-related difference in spontaneous cBRS elicited by isolated muscle metaboreflex activation in healthy humans.

Muscle metaboreflex activation via postexercise ischemia as a tool for teaching cardiovascular physiology for undergraduate students.

The cardiovascular responses to exercise are mediated by several interactive neural mechanisms, including central command, arterial baroreflex, and skeletal muscle mechano- and metaboreflex. In humans, muscle metaboreflex activation can be isolated via postexercise ischemia (PEI), which increases sympathetic nerve activity and partially maintains the exercise-induced increase in arterial blood pressure. Here, we describe a practical laboratory class using PEI as a simple and useful technique to teach cardiovascular physiology. In an undergraduate exercise physiology class ( n = 47), a traditional 4-h lecture was conducted discussing the neural control mechanisms of cardiovascular regulation during exercise. Thereafter, eight students (4 men and 4 women) were selected to participate as a volunteer of a practical laboratory class. Each participant performed 90 s of isometric handgrip exercise at 40% of maximal voluntary contraction, followed by 3 min of PEI. Arterial blood pressure and heart rate were measured by digital monitors at rest and during isometric handgrip, PEI, and recovery. In addition, blood samples were collected from the tip of the exercising finger for blood lactate analyses. After the laboratory class, a survey was given to determine the perceptions of the students. The findings demonstrate that this laboratory class has proved to be highly popular with students, who self-reported a significant improvement in their understanding of several aspects of cardiovascular regulation during exercise.

Blunted cardiovascular responses to exercise in Parkinson's disease patients: role of the muscle metaboreflex.

Patients with Parkinson's disease (PD) exhibit attenuated cardiovascular responses to exercise. The underlying mechanisms that are potentially contributing to these impairments are not fully understood. Therefore, we sought to test the hypothesis that patients with PD exhibit blunted cardiovascular responses to isolated muscle metaboreflex activation following exercise. For this, mean blood pressure, cardiac output, and total peripheral resistance were measured using finger photoplethysmography and the Modelflow method in 11 patients with PD [66 ± 2 yr; Hoehn and Yahr score: 2 ± 1 a.u.; time since diagnosis: 7 ± 1 yr; means ± SD) and 9 age-matched controls (66 ± 3 yr). Measurements were obtained at rest, during isometric handgrip exercise performed at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a cold pressor test was assessed to confirm that blunted cardiovascular responses were specific to exercise and not representative of generalized sympathetic responsiveness. Changes in mean blood pressure were attenuated in patients with PD during handgrip (PD: ∆25 ± 2 mmHg vs. controls: ∆31 ± 3 mmHg; P < 0.05), and these group differences remained during postexercise ischemia (∆17 ± 1 mmHg vs. ∆26 ± 1 mmHg, respectively; P < 0.01). Additionally, changes in total peripheral resistance were attenuated during exercise and postexercise ischemia, indicating blunted reflex vasoconstriction in patients with PD. Responses to cold pressor test did not differ between groups, suggesting no group differences in generalized sympathetic responsiveness. Our results support the concept that attenuated cardiovascular responses to exercise observed in patients with PD are, at least in part, explained by an altered skeletal muscle metaboreflex. NEW & NOTEWORTHY Patients with Parkinson's disease (PD) presented blunted cardiovascular responses to exercise. We showed that cardiovascular response evoked by the metabolic component of the exercise pressor reflex is blunted in patients with PD. Furthermore, patients with PD presented similar pressor response during the cold pressor test compared with age-matched controls. Altogether, our results support the hypothesis that attenuated cardiovascular responses to exercise observed in patients with PD are mediate by an altered skeletal muscle metaboreflex.

GABAergic contribution to the muscle mechanoreflex-mediated heart rate responses at the onset of exercise in humans.

Previous studies have indicated that central GABAergic mechanisms are involved in the heart rate (HR) responses at the onset of exercise. On the basis of previous research that showed similar increases in HR during passive and active cycling, we reasoned that the GABAergic mechanisms involved in the HR responses at the exercise onset are primarily mediated by muscle mechanoreceptor afferents. Therefore, in this study, we sought to determine whether central GABA mechanisms are involved in the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans. Twenty-eight healthy subjects (14 men and 14 women) aged between 18 and 35 yr randomly performed three bouts of 5-s passive and active cycling under placebo and after oral administration of diazepam (10 mg), a benzodiazepine that produces an enhancement in GABAA activity. Beat-to-beat HR (electrocardiography) and arterial blood pressure (finger photopletysmography) were continuously measured. Electromyography of the vastus lateralis was obtained to confirm no electrical activity during passive trials. HR increased from rest under placebo and further increased after administration of diazepam in both passive (change: 12 ± 1 vs. 17 ± 1 beats/min, P < 0.01) and active (change: 14 ± 1 vs. 18 ± 1 beats/min, P < 0.01) cycling. Arterial blood pressure increased from rest similarly during all conditions ( P > 0.05). Importantly, no sex-related differences were found in any variables during experiments. These findings demonstrate, for the first time, that the GABAergic mechanisms significantly contribute to the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans. NEW & NOTEWORTHY We found that passive and voluntary cycling evokes similar increases in heart rate and that these responses were enhanced after diazepam administration, a benzodiazepine that enhances GABAA activity. These findings suggest that the GABAergic system may contribute to the muscle mechanoreflex-mediated vagal withdrawal at the onset of exercise in humans.