Neonatal intermittent hypoxia induces sex‐specific enhancement of hypoxic ventilatory response in rat pups

Abstract

We tested the hypothesis that chronic intermittent hypoxia induces gender‐specific effects on hypoxic ventilatory response (HVR) in newborn rats. Rat pups were exposed with their dams to normal room air (controls) or to chronic intermittent hypoxia (IH: O2 levels cycled between 21% and 5% every 10 minutes for 1h followed by 1h under normoxia, 24h/day) during postnatal days 1–10. Minute ventilation (VE) was measured in 10‐day‐old male and female rat pups using whole‐body plethysmography. To assess HVR, VE was measured in normoxia and during acute hypoxia (5% achieved in 60 seconds), and expressed as % changes vs. baseline. IH induced a growth‐delay of similar magnitude in males and females. Under normoxia, respiratory frequency was slightly lower in both male and female IH rats vs. controls, but VE was similar. In males, HVR was higher in IH rats (+57±13%) vs. controls (+32±8%, p=0,001). In females, HVR was similar between neonatal IH (+35±13%) and control rats (+42±7%, p=ns). This study shows that neonatal IH increases HVR specifically in male rat pups, and suggests that apneas may have sex‐specific effects on respiratory control in neonates. (Founded by FRSQ, Sick kids foundation/CIHR).