Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans

Abstract

Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents.

Lack of effect of ovarian cycle and oral contraceptives on baroreceptor and nonbaroreceptor control of sympathetic nerve activity in healthy women

“…In contrast, during CPT, MSNA responses were not different during differing hormonal phases (10). Jarvis and colleagues (20) examined sympathetic responses to static handgrip exercise and during CPT in non-OCP users during EF and ML phases and in age-matched men. Sympathetic responses during static exercise and posthandgrip circulatory arrest were greater in men than in either hormonal phase in women, which were not different from each other.…”

“…Concomitantly, basal sympathetic nerve activity (SNA) has been shown to follow a cyclical pattern with the ovarian cycle in premenopausal women. Some (27, 31), but not all (3,4,10,12,20,22,23), investigators have previously reported that resting SNA directed to the vascular bed of muscle displays a cyclical pattern in healthy nonsmoking, premenopausal females. Resting muscle sympathetic nerve activity (MSNA) is increased during the ML, high-hormone, phase following ovulation and is decreased during the EF, low-hormone phase during menses.…”

Activation of the carotid chemoreflex secondary to muscle metaboreflex stimulation in men

“…These results support a change in central integration of the carotid chemoreceptor feedback with metaboreflex activation and help explain previous evidence of carotid chemoreceptor activation during exercise despite no increase in circulating carotid chemoreceptor stimuli. Our investigation was only done in young healthy men; however, it would be of interest to investigate the interactions between the metaboreflex and the chemoreflex in young women, particularly considering that the metaboreflex is less sensitive in women (18). It would also be prudent to investigate these interactions in clinical populations such as chronic heart failure as it has been shown to enhance both the metaboreflex (14,24) and chemoreflex (33,36).…”

Short-term administration of progesterone and estradiol independently alter carotid-vasomotor, but not carotid-cardiac, baroreflex function in young women

“…In young women, there have been mixed results as to whether the fluctuations in ovarian hormones alter baroreflex control of sympathetic activity. Minson et al (29) reported an increase in MSNA sensitivity in the mid-luteal phase compared with the early follicular phase using the Modified Oxford method, whereas others have reported no changes across the same menstrual phases using a variety of techniques (6,14,22,27). Similarly, combined oral contraceptives have been shown to either decrease (30) or have no effect on (5, 27) sympathetic baroreflex sensitivity.…”

“…The majority of studies have found no differences in both cardiovagal (8,17,29) and sympathetic (6,14,22) baroreflex sensitivity between the early follicular (low hormone) and mid-luteal (high estrogen and progesterone) phases, but this is not true of all studies (20,42,44). It is possible that estrogen and progesterone have opposing influences on the baroreflex, necessitating study of the individual actions of the hormones.…”