Contrasting effects of estradiol and progesterone on respiratory pattern and hypoxic ventilatory response in newborn male rats.

We tested the hypothesis that postnatal exposure to progesterone or estradiol exerts distinct effects on respiratory control, apnea frequency, and on hypoxic ventilatory response (HVR). To this aim, we assessed breathing pattern using whole body plethysmography in normoxia and during a sustained hypoxic exposure (10% O(2)-30min) in 10-day-old male rats raised by dams implanted with osmotic minipumps delivering either estradiol (E(2), 7.0microgday(-1)), estradiol+progesterone (E(2)+P, 7.0+70microgday(-1)) or vehicle (propylene glycol) at a regular flow rate throughout postnatal days 1-14. Compared to vehicle, E(2) and E(2)+P pups had a reduced ventilation, metabolic rate and rectal temperature. HVR was specifically increased in E(2)+P pups compared to controls and E(2) pups. On the contrary, both E(2) and E(2)+P pups did not reduced metabolism as much as controls during hypoxic exposure, and the decrease in rectal temperature was abolished. Surprisingly, E(2)+P pups showed a dramatic elevation of sigh frequency, while progesterone (in E(2)+P compared to E(2) and Veh pups) reduced apnea frequency. These findings are relevant to better understand the role of placental steroids on respiratory and metabolic control during early development in rats, and could ultimately contribute to a better understanding of specific respiratory control disorders in preterm neonates, which are chronically deprived from placental steroids exposure.

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% O(2)--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.