Sex modulates the ventilatory response to passive limb-induced muscle mechanoreceptor activation during hypoxia in humans.

Sex appears to modulate interactions between neural mechanisms involved in regulating pulmonary ventilation during mild hypoxic exercise. Therefore, we compared pulmonary ventilation responses elicited by isolated and combined stimulation of the carotid chemoreflex and muscle mechanoreflex between males and females. Twenty-eight healthy adults (14 females) underwent four experimental manipulations: 1) normoxic rest (no stimulation), 2) hypoxic rest (carotid chemoreflex stimulation), 3) normoxic passive movement (muscle mechanoreflex stimulation), and 4) hypoxic passive movement (reflexes costimulation). Isocapnia was maintained using a rebreathing system, and hypoxia was induced by breathing 12% oxygen. Passive movement involved 30-s bouts of unilateral knee manipulation at 300°/s, with surface electromyography confirming absence of voluntary muscle contractions. In males, the pulmonary ventilation response to passive limb movement (last 10 s change vs. rest) was greater under hypoxia than normoxia (means ± SD: hypoxia = 3.6 ± 2.0 vs. normoxia = 1.6 ± 2.4 L/min; P = 0.003), whereas no difference was observed in females (hypoxia = 1.9 ± 2.4 vs. normoxia = 2.2 ± 1.5 L/min; P = 1.000). Moreover, pulmonary ventilation remained elevated in males (hypoxia = 2.7 ± 2.4 vs. normoxia = -0.1 ± 2.2; P < 0.001) but not in females (hypoxia = 0.4 ± 3.3 vs. normoxia = 0.5 ± 1.5; P = 1.000), 30 s following passive limb movement under hypoxia. These findings support a synergistic carotid chemoreflex-muscle mechanoreflex interaction in males but not in females. The persistent ventilatory elevation poststimulation indicates that short-term potentiation contributes to this synergistic interaction in males.NEW & NOTEWORTHY Pulmonary ventilation response to passive limb movement is greater under hypoxia than normoxia in males but not in females. These results support a synergistic interaction between the carotid chemoreflex and muscle mechanoreflex in males but not in females. In addition, pulmonary ventilation remains elevated in males but not in females after the cessation of passive limb movement under hypoxia, suggesting that short-term potentiation may be a mechanism mediating this synergistic reflex interaction in males.