Recovery of ventilatory and metabolic responses to hypoxia in neonatal rats after chronic hypoxia

Chronic hypoxia (CH) during postnatal development attenuates the hypoxic ventilatory response (HVR) in mammals, but there are conflicting reports on whether this plasticity is permanent or reversible. This study tested the hypothesis that CH-induced respiratory plasticity is reversible in neonatal rats and investigated whether the initial plasticity or recovery differs between sexes. Rat pups were exposed to 3 d of normobaric CH (12 % O2) beginning shortly after birth. Ventilation and metabolic CO2 production were then measured in normoxia and during an acute hypoxic challenge (12 % O2) immediately following CH and after 1, 4-5, and 7 d in room air. CH pups hyperventilated when returned to normoxia immediately following CH, but normoxic ventilation was similar to age-matched control rats within 7 d after return to room air. The early phase of the HVR (minute 1) was only blunted immediately following the CH exposure, while the late phase of the HVR (minute 15) remained blunted after 1 and 4-5 d in room air; recovery appeared complete by 7 d. However, when normalized to CO2 production, the late phase of the hypoxic response recovered within only 1 d. The initial blunting of the HVR and subsequent recovery were similar in female and male rats. Carotid body responses to hypoxia (in vitro) were also normal in CH pups after approximately one week in room air. Collectively, these data indicate that ventilatory and metabolic responses to hypoxia recover rapidly in both female and male neonatal rats once normoxia is restored following CH.