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

Abstract

Sex differences have been reported in the respective contribution of cardiac output (Q̇) and vascular constriction to the pressor response to isometric handgrip exercise (IHE). Differently from men, the majority of the blood pressure (BP) response to IHE in young women is due to elevated Q̇ rather than elevations in total peripheral resistance (TPR). The underlying mechanisms for these differences are unknown, but previous data suggest that the β‐adrenergic receptors offset α‐adrenergic vasoconstriction in young women under resting condition. Whether this could be extended to an exercise condition remains to be determined. Given this, the aim of the present study was to investigate whether the β‐adrenergic receptors play a pivotal role in sex‐related differences in the BP regulation during ischemic IHE. Ten men (21 ± 0.6 years) and 9 women (23 ± 1.3 years) healthy and physically active volunteers were recruited. All women were non‐oral contraceptives users and performed experiments in the early follicular phase of the menstrual cycle. To make the forearm ischemic prior to exercise, a 3 min period of circulatory arrest was achieved by inflating an upper arm cuff to supra systolic pressure. This cuff remained inflated for 2 min of isometric exercise at 30% of maximal voluntary contraction force, and 2 min of post‐exercise circulatory occlusion (PECO). Beat‐to‐beat heart rate (HR) (electrocardiography) and arterial BP (finger photopletysmography) were continuously measured. Beat‐to‐beat changes in stroke volume (SV) was obtained with Modelflow method and matched with the responses of heart rate (HR) to estimate Q̇ (Q̇=SV x HR) and TPR (TPR=Mean BP/Q). The exercise and PECO responses were analyzed using the peak change. Two trials were randomly conducted in different days either placebo or non‐selective β‐adrenergic blockade (40mg propranolol). During ischemic IHE under placebo condition, mean BP increased from rest in both men and women, however the magnitude of these responses was greater in men. During PECO, the mean BP remained elevated and the sex differences persisted. The β‐adrenergic blockade attenuated the mean BP response during ischemic IHE from rest in men (Δ 51 ± 6 mmHg vs Δ 39 ± 6 mmHg, P<0.01) but not in women (Δ 28 ± 5 mmHg vs Δ 32 ± 5mmHg, P=0.17). This attenuated mean BP response observed in men under β‐blockade could be explained by a reduction in Q̇ (Δ 3.0 ± 0.4l/min vs Δ 1.2 ± 0.2 l/min, P<0.01). This was less pronounced in women (Δ 2.0 ± 0.4 l/min vs Δ 1.0 ± 0.2 l/min, P=0.05). In addition, vascular constriction was increased during ischemic IHE and PECO in men and these responses were not affected by β‐blockade. In contrast, increases in TPR were greater in women under β‐adrenergic blockade during both ischemic IHE (Δ 1.2 ± 0.7 mmHg.L‐1.min vs Δ 3.3 ± 0.9 mmHg.L‐1.min, P=0.03) and PECO (Δ 4.5 ± 0.9 mmHg.L‐1.min vs Δ 6.8 ± 1.1 mmHg.L‐1.min, P=0.04). These findings demonstrate for the first time that the sex differences in arterial BP regulation during ischemic IHE are mediated by β‐adrenergic re...

Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing

“…Another interesting influencing factor that attributes to the different BPR in women compared to men was identified Table 4 Stepwise multivariate regression analyses of the results of the vascular evaluation with the SBP/MET slope, the SBP/W slope and the peak SBP/W ratio as continuous dependent variable for male and female athletes Predictors of the model were brachial systolic BP, brachial diastolic BP, central systolic and diastolic BP, mean central BP, central pulse pressure, PWV, Aix@75 bpm, R and total vascular resistance with different metaboreceptor stimulation in women (Samora et al 2019). Notably, in pre-menopausal women, beta-adrenergic sensitivity is enhanced compared to men which blunts vasoconstrictor response due to concurrent beta-adrenergic mediated vasodilation (Song et al 2020) during constantload submaximal exercise and consequently leads to a limitation in stroke volume (Wheatley et al 2014).…”

Sex differences in muscle activity emerge during sustained low‐intensity contractions but not during intermittent low‐intensity contractions

“…Stimulation of these muscle afferents can limit the voluntary descending drive to the muscle, or directly inhibit motoneurones at the spinal level, to reduce the development of muscle fatigue (Bigland‐Ritchie, Dawson, Dawson, Johansson, & Lippold, 1986; Blain et al, 2016; Garland, 1991; Woods, Furbush, Furbush, & Bigland‐Ritchie, 1987). Limb occlusion, which is known to activate group III/IV afferents, has been used following fatiguing isometric (30% MVC) handgrip exercise to reveal that mechano‐ and metabo‐reflexes differ between men and women (Ettinger et al, 1996; Minahan et al, 2018; Samora, Incognito, Incognito, & Vianna, 2019). In addition, isometric handgrip exercise differs depending on contraception usage, where normally menstruating women have greater fatigue responses to men compared to women taking hormonal contraception (Minahan et al, 2018).…”

Short‐term water deprivation attenuates the exercise pressor reflex in older female adults

“…Finally, while the mechanisms mediating these age‐related changes are unclear, it is possible that the lack of estrogen after menopause reduces β‐adrenergic mediated vasodilation (which normally offsets α‐adrenergic mediated vasoconstriction) , subsequently enhancing SVR. In support of this, propranolol (β‐blocker) increased total peripheral resistance responses during ischemic HG in healthy young female adults, while attenuating cardiac output responses (Samora, Incognito, & Vianna, 1985). Therefore, it is possible that older adults, who have limited capabilities to increase cardiac output during exercise (Empel, Kaye, & Borlaug, 2014; Lalande et al., 2014; Ogawa et al., 1992; Trinity et al., 2018), must rely on SVR to raise BP and provide blood flow to active tissue.…”