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 μg 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 μg kg−1 i.v.) were potent and specific antagonists of the 5‐HT induced rise in blood pressure, while the α‐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 μg 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.

Evidence for 5‐HT1B/1D and 5‐HT2A receptors mediating constriction of the canine internal carotid circulation

“…The mechanisms involved in the vasoconstrictor responses to 5‐HT are complex and include, in addition to direct stimulation of vascular smooth muscle receptors, indirect actions ( Martin, 1994 ). Thus, a 5‐HT 2 receptor‐stimulated release of catecholamines from the canine adrenal medulla ( Feniuk et al ., 1981 ), as well as the release of noradrenaline from sympathetic neurons by a 5‐HT 3 receptor‐mediated depolarisation ( Fozard et al ., 1979 ) can be excluded since zolertine, in doses high enough to block α‐adrenoceptors, failed to antagonize the 5‐HT‐induced internal carotid vasoconstriction ( Vidrio & Hong, 1976 ). In agreement with the latter, the responses to 5‐HT were not blocked by tropisetron (present results), in doses high enough to antagonise both 5‐HT 3 and 5‐HT 4 receptors ( Villalón et al ., 1991 ).…”

The adrenergic stress response in fish: control of catecholamine storage and release

“…In addition to catecholamines, the chromaffin cells of different anuran [68,69,153] and mammalian (see [88] for references) species also contain serotonin. In mammals, several studies have attributed direct peripheral catecholamine-releasing effects to serotonin [73,74,86,236]. However, although the role of the central serotonergic system in the control of the sympathoadrenal system is well documented [48], the physiological significance of the adrenal serotonergic stores in the control of catecholamine release has yet to be elucidated.…”

Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5‐HT in vagosympathectomized dogs

“…However, we have to admit that the mechanisms involved in the vasoconstrictor responses to 5-HT are complex and include, in addition to stimulation of 5-HT,-like and/or 5-HT2 receptors, indirect actions (see Martin, 1994). Thus, a 5-HT2A receptor-stimulated release of catecholamines from the canine adrenal medulla (Feniuk et al, 1981) can be excluded since ritanserin, phentolamine and propranolol failed to antagonize the effects of 5-HT. Likewise, the release of noradrenaline from sympathetic neurones either by a 5-HT3 receptor-mediated depolarization (Fozard et al, 1979) or by a tyramine-like action on these neurones (Humphrey et al, 1983) is also ruled out based on the failure of MDL 72222, tropisetron, fluoxetine and reserpine (in addition to phentolamine and propranolol) to antagonize the responses to 5-HT; similarly, an endothelium-dependent vasoconstriction via the synthesis and release of pro-constrictor cyclo-oxygenase products (Rosenblum & Nelson, 1988;Seager et al, 1992) seems unlikely based on the lack of effect of indomethacin.…”