Prenatal dexamethasone exposure causes loss of neonatal hypoxia tolerance: cellular mechanisms.

Glucocorticoids promote lung cell differentiation and thus enhance surfactant synthesis in the management of neonatal respiratory distress syndrome. Because they also accelerate differentiation in other targets, glucocorticoids may compromise physiologic responses that operate through specialized fetal-neonatal mechanisms. The current study explores one such process, the capacity to maintain cardiac function during hypoxia, a critical function in light of the hypoxia associated with parturition and with neonatal respiratory distress. Pregnant rats were given 0.05, 0.2, or 0.8 mg/kg of dexamethasone on gestational d 17, 18, and 19, and the response to hypoxia was assessed in the offspring on the day after birth. Dexamethasone produced a dose-dependent impairment of survival during exposure to 5% O2 (5 kPa O2) for 120 min. ECG measurements showed that death in the dexamethasone-exposed animals was preceded by multiple arrhythmias and progressive atrioventricular conduction defects, terminating in cardiac arrest. Because maintenance of neonatal cardiac conduction during hypoxia depends on adrenergic mechanisms operating through adrenomedullary catecholamine release and actions at transiently expressed alpha 2-receptors in the immature myocardium, we examined these mechanisms in control and dexamethasone-exposed neonates. Dexamethasone caused cardiac alpha 2-receptors to disappear prematurely, an effect that was selective for this receptor population because no comparable changes were seen in alpha 1-receptors. Under normal circumstances, neonatal adrenomedullary responses to hypoxia operate in the absence of functional sympathoadrenal innervation, and cardiac-sympathetic innervation does not play a significant role; in a similar fashion, the dexamethasone-exposed animals did not display alterations in the functional state of sympathetic innervation of the adrenal medulla or heart at birth.(ABSTRACT TRUNCATED AT 250 WORDS)