Inhibition by nifedipine of endothelin-induced adrenal catecholamine secretion in anesthetized dogs.
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.
Yamaguchi
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Faculté de pharmacie, Université de Montréal, Canada.
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*
D016232:Endothelins; D009543:Nifedipine; D009638:Norepinephrine; D004837:Epinephrine