Menstrual cycle and sex effects on sympathetic responses to acute chemoreflex stress

Abstract

This study aimed to examine the effects of sex (males vs. females) and sex hormones (menstrual cycle phases in women) on sympathetic responsiveness to severe chemoreflex activation in young, healthy individuals. Muscle sympathetic nerve activity (MSNA) was measured at baseline and during rebreathing followed by a maximal end-inspiratory apnea. In women, baseline MSNA was greater in the midluteal (ML) than early-follicular (EF) phase of the menstrual cycle. Baseline MSNA burst incidence was greater in men than women, while burst frequency and total MSNA were similar between men and women only in the ML phase. Chemoreflex activation evoked graded increases in MSNA burst frequency, amplitude, and total activity in all participants. In women, this sympathoexcitation was greater in the EF than ML phase. The sympathoexcitatory response to chemoreflex stimulation of the EF phase in women was also greater than in men. Nonetheless, changes in total peripheral resistance were similar between sexes and menstrual cycle phases. This indicates that neurovascular transduction was attenuated during the EF phase during chemoreflex activation, thereby offsetting the exaggerated sympathoexcitation. Chemoreflex-induced increases in mean arterial pressure were similar across sexes and menstrual cycle phases. During acute chemoreflex stimulation, reduced neurovascular transduction could provide a mechanism by which apnea-associated morbidity might be attenuated in women relative to men.

Keywords: hypercapnia; hypoxia; menstrual cycle; muscle sympathetic nerve activity; sex differences.

Copyright © 2015 the American Physiological Society.

Figures

Fig. 1.

Individual and sample patterns of total muscle sympathetic nerve activity (MSNA) during early-follicular (EF) and midluteal (ML) phases of the menstrual cycle. A: individual data from all women at baseline. ●, Mean ± SD for EF phase; ○, mean ± SD for ML phase. *P < 0.05 vs. EF. B: traces of 15 s of baseline recordings from a representative subject during EF and ML phases. au, Arbitrary units. C: individual data from all women during the 2nd half of apnea (APN-P2). ●, Mean ± SD for EF phase; ○, mean ± SD for ML phase. *P < 0.05 vs. EF. D: traces of end-inspiratory apnea performed during EF and ML phases.

Fig. 2.

Neurovascular transduction. Total peripheral resistance index (TPRi) normalized to total MSNA at baseline was higher in women in the EF than ML phase of the menstrual cycle and men (*P < 0.05 vs. EF). During chemoreflex activation, relative neurovascular transduction tended to be higher in men than in women in the EF (P = 0.06) and ML (P = 0.09) phases of the menstrual cycle, although the difference was not statistically significant. Values are means ± SD. BSL, baseline.

Fig. 3.

Respiratory characteristics. Respiration rates and end-tidal Po2 values were similar between all groups. End-tidal Pco2 values were higher in men than in women in the ML phase of the menstrual cycle and higher during the EF than the ML phase. Values are means ± SD. REBR, rebreathing; POST, postapnea.

Fig. 4.

Relative sympathoexcitation during chemoreflex stimulation. Total MSNA and burst frequency were increased to the greatest extent in women in the EF phase. Increase in burst amplitude was greater in the EF than ML phase but was not different between sexes. In women, a statistical interaction between menstrual cycle phase and chemoreflex condition was observed in the burst amplitude response: *P < 0.05, EF vs. ML. Values are means ± SD. APN-P1, 1st half of apnea.

Fig. 5.

Relative changes in hemodynamics during chemoreflex stimulation. Significant changes in mean arterial pressure (MAP) and total peripheral resistance index (TPRi) occurred across chemoreflex stimuli. Relative changes in MAP and TPRi, as well as cardiac index (Q̇i) and heart rate (HR), were not significantly different between sexes or menstrual cycle phases. Values are means ± SD.