Implication of L-type Ca2+ channels in noncholinergic adrenal catecholamine secretion by endothelin-1 in vivo.
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 microgram given to the gland or approximately 0.0197 microgram/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 15-30 min. In the second group treated with nifedipine (5 micrograms or approximately 0.207 microgram/kg) similarly administered 10 min before 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 approximately 0.041 mg/kg) or atropine (0.5 mg or approximately 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. Furthermore, 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.
Yamaguchi
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Faculté de Pharmacie, Université de Montréal, Québec, Canada.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002319:Cardiovascular System / Q000187:drug effects; D018678:Cholinergic Agents / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010425:Pentolinium Tartrate / Q000494:pharmacology
D015220:Calcium Channels; D018678:Cholinergic Agents; D016232:Endothelins; D001285:Atropine; D010425:Pentolinium Tartrate; D009543:Nifedipine; D009638:Norepinephrine; D004837:Epinephrine