Effects of prenatal cocaine exposure on development of rat cardiac adrenergic receptors and their control of adenylate cyclase activity
Fetal exposure to cocaine is associated with increased perinatal cardiac risk. Because cocaine promotes adrenergic actions, we assessed the effects of cocaine on development of cardiac adrenergic receptors and cell signaling in the rat. Pregnant rats were given 30 mg/kg s.c. of cocaine from gestational day 8 through 20 and the ontogenetic patterns of adrenergic receptor subtypes and their linkage to control of adenylate cyclase activity were assessed from birth to adulthood. Neonatal overexpression of α2-receptors is required for maintenance of cardiac conduction during the hypoxia associated with birth or sleep apnea, and these receptors were present equally in both control and cocaine-exposed animals; the ontogenetic disappearance of α2-receptors also was unaffected by drug exposure. Similarly, the acquisition of cardiac β- adrenergic receptors, their link to adenylate cyclase activity, and the development of adenylate cyclase catalytic units (assessed with forskolin) remained essentially normal despite fetal cocaine exposure. These results suggest that adverse effects on perinatal cardiac function associated with human maternal cocaine abuse either result from indirect actions of cocaine, such as cell damage caused by hypoxia/ischemia, or alternatively from primary contributions of covariables known to affect cardiac development, such as cigarette smoking.
