This study investigates the effects of prenatal corticosteroid administration on newborn sympathoadrenal mechanisms involved in postnatal adaptation. Randomly assigned preterm (122-125 days) fetal sheep were treated with hydrocortisone or saline for 60 h and delivered by cesarean section. We examined postnatal physiological adaptation, sympathoadrenal responses, cardiac beta-receptor density, and the receptor-cyclase system. We observed increased ventilatory, cardiovascular, and metabolic responses function in the corticosteroid-treated animals despite a marked attenuation in the anticipated surge of plasma catecholamine concentrations and a decrease in epinephrine secretion rate, which is normally seen at birth. Myocardial beta-adrenergic receptor density and affinity states were comparable in both groups. Basal and agonist-mediated adenylyl cyclase activity in myocardial tissue was increased in the corticosteroid-treated animals. We speculate that the increase in myocardial adenylyl cyclase activity may be accompanied by similar changes in other organ systems and that this could account for the augmentation in respiratory, cardiovascular, and metabolic responses in the corticosteroid-treated animals.
The intrauterine clearance rate of catecholamines is higher than in newborn animals or in adults. The separate contributions of the fetus and placenta to this clearance are not known. The placenta is a site of expression of the amine plasma membrane transporters that mediate this process. To determine the physiological role of this placental transporter in vivo, we studied fetal sheep at 123 days with common umbilical vein (UV), fetal arterial (AO), and venous catheters. Tritiated norepinephrine ([3H]NE) was infused to determine the kinetics of placental and fetal NE appearance and clearance rates. Umbilical flow was determined by [3H]NE infusion. Placental and total (fetal-placental) NE clearance rates were determined by measurement of [3H]NE from simultaneously drawn UV and AO samples. Total clearance was 99 +/- 8 ml.kg-1.min-1. Placental fractional [3H]NE extraction was 21% and accounted for 48% of total clearance. Fetal plasma NE production rate was 85 +/- 20 ng.kg-1.min-1. We conclude that placental catecholamine clearance is an important metabolic function of the placenta. This mechanism for clearance of the high fetal production rate of catecholamines is vital for fetal homeostasis. We speculate that derangements in placental catecholamine clearance may explain the exaggerated adverse effects on the fetus of drugs like cocaine, which block catecholamine transport.
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