Implication of l-type ca2+ channels in noncholinergic adrenal
catecholamine secretion by endothelin-1 in vivo.
Yamaguchi, Nobuharu.
Groupe de Recherche sur le Syst[grave]eme Nerveux Autonome,
Facult[acute]e de Pharmacie, Universit[acute]e de Montr[acute]eal,
Montr[acute]eal, Qu[acute]ebec H3C 3J7, Canada
APStracts 2:0058R, 1995.
The aim of the present study was to investigate if either
dihydropyridine-sensitive L-type Ca2+ channels or cholinergic
receptor-mediated mechanisms are implicated in endothelin-1 (ET)
-induced adrenal catecholamine (CA) secretion in anesthetized dogs. ET
was locally administered to the left adrenal gland via the left
adrenolumbar artery. Plasma CA concentrations in adrenal venous and
aortic blood were determined by a high-performance liquid
chromatography method. In the control group, local infusion (1 min,
0.5 ml/min) of ET (the fixed total dose of 0.5 Ng given to the gland
or 0.0197 Ng/kg of body weight) resulted in a sharp increase in the
basal CA output, followed by a rapid decline and a relatively slow
secondary response lasted over a period of 15 to 30 min. In the
second group treated with nifedipine (5 Ng or 0.207 Ng/kg) similarly
administered 10 min prior to ET infusion, the ET-induced first steep
increase in CA output was significantly attenuated by approximately
75% (P < 0.05, n = 6). In dogs similarly receiving either pentolinium
(1 mg or 0.041 mg/kg) or atropine (0.5 mg or 0.018 mg/kg), the ET
-induced CA response remained unchanged. The results indicate that ET
-induced adrenal CA release was largely mediated by the activation of
dihydropyridine-sensitive L-type Ca2+ channels. Further, neither
nicotinic nor muscarinic receptors were functionally implicated in
the CA response to ET. The study suggests the existence of
noncholinergic mechanisms involved in the secretory action of ET on
the adrenal medulla in the dog in vivo.
Received 17 June 1994; accepted in final form 15 February 1995.
APS Manuscript Number R338-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 7 March 1995.