We tested the hypothesis that differences in sympathetic reflex responses to head-up tilt (HUT) between males (n = 9) and females (n = 8) were associated with decrements in postural vasomotor responses in women. Muscle sympathetic nerve activity (MSNA; microneurography), heart rate, stroke volume (SV; Doppler), and blood pressure (Finapres) were measured during a progressive HUT protocol (5 min at each of supine, 20 degrees, 40 degrees, and 60 degrees ). MSNA and hemodynamic responses were also measured during the cold pressor test (CPT) to examine nonbaroreflex neurovascular control. SV was normalized to body surface area (SV(i)) to calculate the index of cardiac output (Q(i)), and total peripheral resistance (TPR). During HUT, heart rate increased more in females versus males (P < 0.001) and SV(i) and Q(i) decreased similarly in both groups. Mean arterial pressure (MAP) increased to a lesser extent in females versus males in the HUT (P < 0.01) but increases in TPR during HUT were similar. MSNA burst frequency was lower in females versus males in supine (P < 0.03) but increased similarly during HUT. Average amplitude/burst increased in 60 degrees HUT for males but not females. Both males and females demonstrated an increase in MAP as well as MSNA burst frequency, mean burst amplitude, and total MSNA during the CPT. However, compared with females, males demonstrated a greater neural response (DeltaTotal MSNA) due to a larger increase in mean burst amplitude (P < 0.05). Therefore, these data point to gender-specific autonomic responses to cardiovascular stress. The different MSNA response to postural stress between genders may contribute importantly to decrements in blood pressure control during HUT in females.

Obstructive sleep apnea (OSA) is associated with oscillations of arterial blood pressure (BP) that occur in phase with irregularities of respiration. To explore the role of the sympathetic nervous system in these responses, we studied muscle sympathetic nerve activity (MSNA; peroneal microneurography), an index of vasoconstrictor nerve traffic, and BP during awake regular breathing and during spontaneous apneas in patients with OSA. To determine the role of the arterial chemoreflex, we also examined the effects of 100% O2 (hyperoxia) on MSNA and BP. In awake regularly breathing patients with OSA (n = 12), resting MSNA was markedly higher than in an age-matched control population (n = 15) [41 +/- 23 (SD) vs. 24 +/- 17 bursts/min; P < 0.05] and was unchanged during hyperoxia (n = 9). Apneas during sleep (n = 8) were associated with surges in MSNA followed by transient rises in BP when breathing resumed. In contrast to room air apneas, hyperoxic apneas of similar duration were associated with attenuated MSNA responses (+82 +/- 84% vs. +5 +/- 25% compared with awake baseline; P < 0.05; n = 6), even though O2 did not affect sleep stage and the occurrence of arousal. Thus the BP oscillations that occur with apnea during sleep may in part be mediated by intermittent surges of sympathetic activity resulting in vasoconstriction. Because the MSNA responses to obstructive apnea are blunted during O2 administration, they appear to be linked to intermittent arterial hypoxemia and stimulation of arterial chemoreceptors.

We compared reflex responses to static handgrip at 30% maximal voluntary contraction (MVC) in 26 untrained men (mean age 35 +/- 3 yr) and 23 untrained women (mean age 39 +/- 4 yr). Women demonstrated attenuated increases in blood pressure and muscle sympathetic nerve activity (MSNA; by microneurography) compared with men. This difference was also observed during a period of posthandgrip circulatory arrest. 31P-nuclear magnetic resonance (NMR) spectroscopy studies demonstrated attenuations in the production of diprotonated phosphate and the development of cellular acidosis in women compared with men. Subjects also performed ischemic handgrip to fatigue. During this paradigm, MSNA responses were similar in the two groups, suggesting that freely perfused conditions are necessary for the full expression of the gender effect. Finally, we examined MSNA responses to adductor pollicus exercise in 7 men (26 +/- 1 yr) and 6 women (25 +/- 2 yr). MVC values and times to fatigue were similar in the two groups (MVC: men, 4.3 +/- 0.4 kg; women, 4.0 +/- 0.3 kg; not significant. Time to fatigue: men, 209 +/- 16 s; women, 287 +/- 50 s; not significant). At periods of end exercise and postexercise circulatory arrest, MSNA responses were attenuated in the women compared with the men. We conclude that, during nonischemic static exercise, sympathetic neural outflow is less in women compared with men. This response is due to an attenuated metaboreflex in women. Finally, on the basis of the adductor pollicus experiments, this effect appears independent of muscle mass, workload, and the level of training.