Nitric oxide effect on 5-hydroxytryptamine-induced vasoconstrictions of isolated smooth muscle.

The aim of the present study was to investigate a nitric oxide (NO) involvement in the mediation of a 5-HT-induced vasoconstriction response in the rat portal vein in vitro. Isolated rat portal vein segments were placed in organ baths for isometric force measurement. 5-HT (3 x 10(-8) M-3 x 10(-4) contracted portal vein preparations (EC50 = 7 x 10(-7) M) in a concentration-dependent manner. The vasoconstriction induced by 5-HT was significantly increased in endothelium-denuded vessels. Pretreatment with Nomega-nitro-L-arginine methyl ester (L-NAME 100 microM) enhanced the contractive response to 5-HT either in intact or endothelium-denuded vessels. However, ketanserin (0.1 microM) abolished 5-HT-induced vasoconstrictions (EC50 = 4.6 x 10(-8) M). Furthermore, a non-selective 5-HT(1B/D) receptor agonist, sumatriptan (1 x 10(-10) M-1 x 10(-5) M), induced a reduction of spontaneous rhythmic contractions also in endothelium-intact vessels. However, 5-HT- induced vasoconstriction was unaffected by propranolol (10 microM). The data support the hypothesis of the existence of serotonergic innervations modulating the contractility of vascular smooth muscle. These findings are consistent with the hypothesis that the vasoconstrictor activity of 5-HT in smooth muscle was mediated by activation of 5-HT(1B/D) and 5-HT(2B) receptor subtypes involving the endothelium-dependent mechanism.