Fetal adrenal medulla catecholamine response to hypoxia-direct and neural components

In the fetus, the adrenal medullary catecholamine responses to hypoxia are mediated by direct and neural mechanisms. The present study determined the maturation of these responses in unanesthetized ovine fetuses from 109 to 136 days gestation. In intact fetuses at 109-119 days gestation, hypoxia lowered arterial PO2 from 23.4 +/- 0.9 to 9.5 +/- 0.4 mmHg and induced acute increases in plasma norepinephrine (P less than 10(-5)) and epinephrine (P less than 10(-5)) concentrations. Fetuses at 130-136 days gestation showed similar changes in PO2 and plasma catecholamines as in younger fetuses. Blockade of neural input to the adrenal by hexamethonium (25 mg/kg) reduced but did not eliminate the increases in plasma norepinephrine and epinephrine concentrations in fetuses at 109-119 days gestation, while it completely abolished these responses in fetuses at 130-136 days gestation. These results suggest that in unanesthetized ovine fetuses a direct response of the adrenal medulla to hypoxia is present at 110 days gestation. In contrast, at 130 days gestation the response to hypoxia is entirely neurally mediated. Thus neural innervation to the ovine fetal adrenal medulla matures before 110 days gestation, much earlier than previously reported.