Young women are more susceptible to orthostatic intolerance than men, though the sex-specific pathophysiology remains unknown. As blood pressure (BP) is regulated through the baroreflex mechanism, we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) during orthostasis is impaired in women and can be affected by the menstrual cycle. MSNA and haemodynamics were measured supine and during a graded upright tilt (30 deg for 6 min, 60 deg for 45 min or till presyncope) in 11 young men and 11 women during the early follicular (EFP) and mid-luteal phase (MLP) of the menstrual cycle. Sympathetic baroreflex sensitivity was quantified using the slope of the linear correlation between total activity and diastolic BP during spontaneous breathing. Baroreflex function was further assessed during a Valsalva manoeuvre (VM). Although MSNA burst frequency responses during tilting were similar between sexes and menstrual phases, increases in total activity were lower in women during EFP than MLP (P = 0.030), while total peripheral resistance and plasma noradrenaline were not similarly lower; upright total activity tended to be lower in women during EFP than men (P = 0.102). Sympathetic baroreflex sensitivity did not differ between sexes (P = 0.676) supine (−281 ± 46 (s.e.m.) units beat −1 mmHg −1 in men vs −252 ± 52 in EFP and −272 ± 40 in MLP in women), at 30 deg tilt (−648 ± 129 vs −611 ± 79 and −487 ± 94), and at 60 deg tilt (−792 ± 135 vs −831 ± 92 and −814 ± 142); this sensitivity was not affected by the menstrual cycle (P = 0.747). Similar sympathetic baroreflex sensitivity between sexes and phases was also observed during the VM. Cardiovagal baroreflex sensitivity assessed during decreasing BP (i.e. early phase II of the VM) was comparable between sexes, but it was greater in men than women during increasing BP (i.e. phase IV); the menstrual cycle had no influences on cardiovagal baroreflex sensitivity. We conclude that the menstrual cycle affects sympathetic neural responses but not sympathetic baroreflex sensitivity during orthostasis, though upright vasomotor sympathetic activity is not clearly different between men and women. Not only sympathetic but also cardiovagal baroreflex sensitivity is similar between sexes and menstrual phases during a hypotensive stimulus. However, cardiovagal baroreflex-mediated bradycardia during a hypertensive stimulus is different between sexes but not affected by the menstrual cycle. Thus, other factors rather than sympathetic baroreflex control mechanisms contribute to sex differences in orthostatic tolerance in young humans.

We tested the hypothesis that women have blunted sympathetic neural responses to orthostatic stress compared with men, which may be elicited under hypovolemic conditions. Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in eight healthy young women and seven men in supine position and during 6 min of 60 degrees head-up tilt (HUT) under normovolemic and hypovolemic conditions (randomly), with approximately 4-wk interval. Acute hypovolemia was produced by diuretic (furosemide) administration approximately 2 h before testing. Orthostatic tolerance was determined by progressive lower body negative pressure to presyncope. We found that furosemide produced an approximately 13% reduction in plasma volume, causing a similar increase in supine MSNA in men and women (mean +/- SD of 5 +/- 7 vs. 6 +/- 5 bursts/min; P = 0.895). MSNA increased during HUT and was greater in the hypovolemic than in the normovolemic condition (32 +/- 6 bursts/min in normovolemia vs. 44 +/- 15 bursts/min in hypovolemia in men, P = 0.055; 35 +/- 9 vs. 45 +/- 8 bursts/min in women, P < 0.001); these responses were not different between the genders (gender effect: P = 0.832 and 0.814 in normovolemia and hypovolemia, respectively). Total peripheral resistance increased proportionately with increases in MSNA during HUT; these responses were similar between the genders. However, systolic blood pressure was lower, whereas diastolic blood pressure was similar in women compared with men during HUT, which was associated with a smaller stroke volume or stroke index. Orthostatic tolerance was lower in women, especially under hypovolemic conditions. These results indicate that men and women have comparable sympathetic neural responses during orthostatic stress under normovolemic and hypovolemic conditions. The lower orthostatic tolerance in women is predominantly because of a smaller stroke volume, presumably due to less cardiac filling during orthostasis, especially under hypovolemic conditions, which may overwhelm the vasomotor reserve available for vasoconstriction or precipitate neurally mediated sympathetic withdrawal and syncope.

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.