The Effect of Menstrual Cycle Phase on Neural Recruitment Patterns during Acute Chemoreflex Stress

Abstract

We have shown previously that muscle sympathetic nerve activity (MSNA) responses to acute chemoreflex stress are augmented during the early follicular (EF) phase of the menstrual cycle relative to the midluteal (ML) phase in young healthy women. Interestingly, these differences were most pronounced in terms of MSNA burst amplitude, which may imply that neural recruitment strategies are affected by menstrual cycle phase. Therefore, the purpose of this retrospective analysis was to test the hypothesis that the recruitment of large action potential (AP) clusters occurs to a greater extent during the EF phase of the menstrual cycle compared with the ML phase. MSNA data (microneurography) from 7 young healthy women (aged 23±3 years; body mass index 23±3 kg/m2) were examined at rest and during a voluntary end‐inspiratory apnea which followed a rebreathing protocol to an end‐tidal PO2 of 65 Torr. These data were collected during the EF and ML phases. APs were identified from the filtered MSNA signal using a custom wavelet deconstruction approach which quantified AP firing frequencies (overall AP frequency and AP content per integrated burst). The identified APs were also binned in accordance to peak to peak amplitude to determine individual AP clusters (Scott’s rule). Resting AP frequency and AP content per MSNA burst were not different between menstrual cycle phases (APs/min: P=0.23; APs/burst: P=0.26). Similarly, the number of identified AP clusters at rest did not differ between the EF and ML phases (8±4 vs10±4 clusters; P=0.16). During apnea, changes in AP frequency and AP content per MSNA burst (i.e. expressed relative to baseline) were greater during the EF phase than the ML phase (ΔAPs/min: P=0.02; ΔAPs/burst: P=0.02). Similarly, apnea‐induced recruitment of new AP clusters (i.e. clusters which were not activated at baseline) was greater during the EF phase compared to the ML phase (ΔAP clusters: +6±8 vs+2±6 clusters; P=0.009). Taken together, these findings confirm that augmented integrated MSNA reactivity to chemoreflex stress during the EF phase of the menstrual cycle is mediated by a greater recruitment of latent subpopulations of larger sympathetic neurons relative to the ML phase. We speculate that the change in the gonadal hormone profile between EF (i.e. low estradiol, progesterone) and ML (i.e. elevated estradiol and progesterone) may be associated with centrally‐mediated alterations to neural outflow during chemoreflex stress, although further research is certainly required to address this hypothesis.