The non-neurogenic catecholamine response of the fetal adrenal to hypoxia is dependent on activation of voltage sensitive Ca2+ channels

We have investigated thc cellular mechanisms underlying the catecholamine response of the fetal sheep adrenal to hypoxia before and after the development of adrenal innervation, Adrenals were collected before(80-100 days gestation: n = 7) and after (135-146 days gestation: n = 10) development of innervation and retrogradely perfused with oxygenated (Krebs bicarbonate buffer in vitro via the renal vein, Adrenal hypoxia was induced bg perfusion with hypoxic Krebs buffet (pO(2)=46.7+/-2.4 mm Hg) for 30 min periods in the presence and absence of hexamethonium (500 mu M), Ca2+ (2.5 mM), nifedipine (I mu M) and KCI (10 mM). Hypoxia stimulated an increase (P < 0.001) in the output oi noradrenaline at 80-100 days (3 min pre hypoxia. 0.18+/-0.07 nmol/3 min; 20 min hypoxia, 0.74+/-0.22 nmol/3 min) and at 135-146 days (3 min pre hypoxia, 0.53+/-0.20 nmol/3 min; 20 min hypoxia, 1.71+/-0.85 nmol/3 min). Adrenaline output was also higher (P < 0.001) than basal values (80-100 days, 0.11+/-0.06 nmol/3 min; 135-146 days, 0.53+/-0.15 nmol/3 min) after 20 min hypoxia (0.41+/-0.20 nmol/3 min and 1.35+/-0.56 nmol/3 min respectively). The catecholamine responses to hypoxia were abolished by removal of Ca2+ from the adrenal perfusate. There was a reduction (P < 0.05) in the catecholamine secretory response to hypoxia in the presence of nifedipine. Noradrenaline output decreased from 4.33+/-0.84 nmol/30 min to 0.16+/-0.49 nmol/30 min and adrenaline output decreased from 3.16+/-1.66 nmol/30 min to -0.01+/-0.24 nmol/30 min in the presence of nifedipine. The fetal adrenal secretes catecholamines by a direct or non-neurogenic mechanism in response to hypoxia. This secretory, response is dependent on the activation of voltage sensitive Ca2+ channels in the chromaffin cell membrane.