An analysis of the mechanism of 5-hydroxytrypt-amine-induced vasopressor responses in ganglion-blocked anaesthetized dogs

Abstract

5-Hydroxytryptamine (5-HT) administered intravenously (i.v., 1--30 micrograms kg-1) to ganglion-blocked anaesthetized dogs produced dose-related increases in diastolic blood pressure and we have analysed the mechanism involved. Cyproheptadine and methysergide (10--100 micrograms kg-1 i.v.) were potent and specific antagonists of the 5-HT induced rise in blood pressure, while the alpha-adrenoceptor blocking agent phentolamine (0.3--3 mg kg-1 i.v.) also caused dose-related inhibition. Syrosingopine pretreatment converted the vasopressor action of 5-HT to a vasodepressor action and acute bilateral adrenalectomy caused a marked reduction in the 5-HT-induced rise in blood pressure. In two dogs, 5-HT (30 micrograms kg-1 i.v.) markedly increased the venous plasma concentrations of noradrenaline and adrenaline. We concluded that the 5-HT-induced rise in diastolic pressure in the ganglion blocked anaesthetized dog is due largely to the release of catecholamines of which a substantial component is from the adrenal gland. The rise in diastolic blood pressure is specifically blocked by low doses of cyproheptadine and methysergide suggesting that the release of catecholamines is mediated by specific 5-HT receptors located mainly within the adrenal medulla.