The effects of sex and menstrual cycle phase on sympathetic action potential recruitment patterns during hypercapnic-hypoxic apnea

Abstract

Previously, we demonstrated that integrated muscle sympathetic nerve activity (MSNA) responses to acute chemoreflex stress were augmented during the early follicular (EF) phase of the menstrual cycle relative to both the midluteal (ML) phase and males. These differences were most pronounced in the amplitude component of MSNA, suggesting EF-driven increases in action potential (AP) recruitment in females. Therefore, we tested the hypothesis that neural recruitment, quantified as MSNA AP discharge patterns during acute chemoreflex stress, is potentiated during EF. We retrospectively analyzed MSNA data from 9 young males and 7 young females tested during the EF and ML phases at rest and during a voluntary end-inspiratory hypercapnic-hypoxic apnea. Sympathetic AP discharge patterns were analyzed using wavelet-based methodology. Apnea-driven increases in AP frequency and AP content per integrated burst were greater in EF relative to ML (APs/min: P = 0.02; APs/burst: P = 0.03) and to males (APs/min: P = 0.04; APs/burst: P = 0.02). The recruitment of new larger AP clusters was greater in EF than ML (P < 0.01) but not different from males (P = 0.50). Interestingly, we observed a positive association between the magnitude of change in the estrogen/progesterone ratio from EF to ML and the change in AP cluster recruitment, as both decreased from EF to ML (R² = 0.82; P < 0.01). This suggests that the enhanced progesterone dominance over estrogen during ML may blunt the recruitment of new larger APs. Overall, these data indicate that both sex and the menstrual cycle impact AP recruitment patterns in a manner which may be mediated, at least in part, by gonadal hormones.

Keywords: Action potential recruitment; Chemoreflex; Menstrual cycle; Muscle sympathetic nerve activity; Sex differences.