Inhibition by nifedipine of endothelin-induced adrenal catecholamine secretion in anesthetized dogs.

Abstract

The present study was conducted to investigate local effects of endothelin-1 (ET-1) on basal adrenal catecholamine (CA) secretion and underlying mechanisms of action of ET-1 in anesthetized dogs. ET-1 was locally administered to the left adrenal gland through a catheter inserted into the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. The local infusions (1 min, 0.5 mL/min) of ET-1, in doses of 0.01, 0.1, and 1.0 microgram/mL, resulted in a dose-dependent increase in epinephrine secretion, rising from an initial basal value of 6.9 +/- 1.4 ng.min-1 x g-1 to maximum values of 7.6 +/- 1.5, 81.1 +/- 38.3*, and 680.9 +/- 107.6* ng.min-1 x g-1 (*p < 0.05, n = 7), respectively. Neither mean arterial pressure nor plasma CA levels in aortic blood altered following ET-1 infusions. A similar dose-dependent increase in norepinephrine output was also observed with ET-1. Following the initial peak observed during infusion with the highest dose of ET-1, the output of both epinephrine and norepinephrine remained significantly elevated over a period of 30 min. This ET-1-induced, long-lasting increase in adrenal CA output was abolished by nifedipine (100 micrograms/mL) similarly administered 10 min before ET-1 infusion. The results indicate that ET-1 directly enhances the basal secretion of CA from dog adrenal medulla in vivo. The study suggests that the ET-1-induced increase in adrenal CA secretion is, at least in part, mediated by the opening of dihydropyridine-sensitive L-type calcium channels at the level of adrenal medullary chromaffin cells.