Sex differences in the sympathetic neurocirculatory responses to chemoreflex activation

The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29 ± 6 years, 22.8 ± 2.4 kg/m² : mean ± SD) and 10 men (30 ± 7 years, 24.8 ± 3.2 kg/m² ) undertook randomized 5 min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O₂ ); peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO₂ ), 50% O₂ ; central chemoreflex activation) and hypercapnic hypoxia (7% CO₂ , 10% O₂ ; central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; finger photoplethysmography) and minute ventilation ( $\dot{V}$_E ; pneumotachometer) were measured. Total MSNA (P = 1.000 and P = 0.616), MAP (P = 0.265) and $\dot{V}$_E (P = 0.587 and P = 0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in $\dot{V}$_E during hypercapnic hyperoxia (27.3 ± 6.3 vs. 39.5 ± 7.5 l/min, P < 0.0001) and hypercapnic hypoxia (40.9 ± 9.1 vs. 53.8 ± 13.3 l/min, P < 0.0001) compared with men. However, total MSNA responses were augmented in women (hypercapnic hyperoxia 378 ± 215 vs. 258 ± 107%, P = 0.017; hypercapnic hypoxia 607 ± 290 vs. 362 ± 268%, P < 0.0001). No sex differences in total MSNA, MAP or $\dot{V}$_E were observed during isocapnic hyperoxia and hypocapnic hyperoxia. Our results indicate that young women have augmented sympathetic responses to central chemoreflex activation, which explains the augmented MSNA response to combined central and peripheral chemoreflex activation. KEY POINTS: Sex differences in the control of breathing have been well studied, but whether there are differences in the sympathetic neurocirculatory responses to chemoreflex activation between healthy women and men is incompletely understood. We observed that, compared with young men, young women displayed augmented increases in muscle sympathetic nerve activity during both hypercapnic hyperoxia (central chemoreflex activation) and hypercapnic hypoxia (central and peripheral chemoreflex activation) but had attenuated increases in minute ventilation. In contrast, no sex differences were found in either muscle sympathetic nerve activity or minute ventilation responses to isocapnic hypoxia (peripheral chemoreceptor stimulation). Young women have blunted ventilator, but augmented sympathetic responses, to central (hypercapnic hyperoxia) and combined central and peripheral chemoreflex activation (hypercapnic hypoxia), compared with young men. The possible causative association between the reduced ventilation and heightened sympathetic responses in young women awaits validation.