Regional vascular effects of serotonin and ketanserin in young, healthy subjects.

Abstract

The local hemodynamic effects of serotonin (5-hydroxytryptamine; 5-HT) and the selective 5-HT2 antagonist ketanserin were investigated in the forearm of 20 healthy volunteers. Single doses of 5-HT (0.1-80 ng/kg/min) and ketanserin (5-125 ng/kg/min) were administered intra-arterially. The relative .alpha.1-adrenergic receptor and 5-HT2 blocking potencies of ketanserin were investigated using intra-arterial infusion of cumulative doses of methoxamine (0.1, 0.3, and 0.5 .mu.g/kg/min), tyramine (0.25, 0.50, and 1.25 .mu.g/kg/min), and 5-HT (10, 30, and 80 ng/kg/min) together with a low dose (5 ng/kg/min) and a high dose (50 ng/kg/min) of ketanserin. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded semicontinuously. Intra-arterial infusion of 5-HT induced an initial transient vasodilatation, followed by a steady vasodilatation for the low doses of 5-HT (0.1-10 ng/kg/min; p < 0.05). A steady vasoconstriction was only obtained at the highest dose of 5-HT. Ketanserin induced a dose-dependent increase in forearm blood flow from 15 ng/kg/min (p < 0.05) onward. The vasodilatation induced by 5-HT (1 ng/kg/min) was significantly enhanced by ketanserin (125 ng/kg/min; p < 0.05), whereas the vasoconstriction elicited by 5-HT (80 ng/kg/min) was reversed by ketanserin (50 ng/kg/min; p < 0.05), thus confirming that 5-HT2 receptors were stimulated by 5-HT. In this model ketanserin proved to be a more potent antagonist of .alpha.1-adrenergic receptors than of 5-HT2 receptors, since the vasoconstriction induced by methoxamine and tyramine was reduced by a lower dose of ketanserin than was the vasoconstriction induced by 5-HT. It is concluded that 5-HT acts predominantly as a vasodilator in healthy subjects, probably by 5-HT1-like receptor stimulation. Only at high doses of 5-HT did vasoconstriction mediated by 5-HT2 receptor stimulation occur. The vasodilatation induced by ketanserin was due most likely to its .alpha.1-adrenergic blocking properties.