Progesterone increases hypoxic ventilatory response and reduces apneas in newborn rats

We hypothesized that progesterone may enhance the hypoxic ventilatory response and reduce the occurrence of apneas in newborn male rats. We studied 10-day-old rats chronically exposed to progesterone (Prog) or vehicle through the milk of lactating mothers. Respiratory and metabolic recordings were performed using whole body plethysmography under normoxia and during hypoxic exposure (10% O2—30 min). While progesterone did not alter baseline breathing and metabolic rate, it increased hypoxic ventilatory response particularly by limiting the magnitude of the ventilatory roll-off during the second phase of the hypoxic ventilatory response (i.e. following 5 min of exposure). In parallel, progesterone lowered the number of spontaneous apneas and drastically reduced the occurrence of post-sigh apneas during hypoxic exposure by limiting the time of the post-sigh expiratory pause. Following domperidone injection (used to block peripheral D2 dopamine receptor), minute ventilation increased in Veh pups and the number of spontaneous apneas decreased. These responses were not observed in Prog pups, suggesting that progesterone reduces peripheral dopaminergic inhibition on breathing. We conclude that progesterone is a potent stimulant of hypoxic ventilatory response in newborn rats and effectively reduces the occurrence of apneas.