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 catecholam ine response of the fetal sheep adrenal to hypoxia before and after th e development of adrenal innervation, Adrenals were collected before(8 0-100 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 hypoxi a 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 hexamethoniu m (500 mu M), Ca2+ (2.5 mM), nifedipine (I mu M) and KCI (10 mM). Hypo xia 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 hypo xia, 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). Adrena line 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 resp ectively). The catecholamine responses to hypoxia were abolished by re moval of Ca2+ from the adrenal perfusate. There was a reduction (P < 0 .05) in the catecholamine secretory response to hypoxia in the presenc e 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 o f nifedipine. The fetal adrenal secretes catecholamines by a direct or non-neurogenic mechanism in response to hypoxia. This secretory, resp onse is dependent on the activation of voltage sensitive Ca2+ channels in the chromaffin cell membrane.