Can peripheral serotonergic blockade explain the hypotensive effect of ketanserin?

Serotonin (5-hydroxytryptamine) causes contraction of most large blood vessels and of venules. This is due mainly to direct activation of the smooth muscle or to amplification of the response to other neurohumoral mediators. Vasodilator responses to serotonin are seen mainly at the arteriolar level. They can be due to the release of other endogenous vasodilators, direct relaxation of vascular smooth muscle, inhibition of adrenergic neurotransmission, or release of an endothelium-dependent relaxing factor(s). Aggregating platelets release enough serotonin to evoke both constrictor and dilator responses. Hence the absence of endothelial cells or of adrenergic nerve activity may change the response to platelets from dilatation to constriction. Vasoconstrictor responses to serotonin released from aggregating platelets may play a role in the maintenance of the augmented peripheral resistance in hypertension. Such an involvement of serotonin is suggested by the following observations in humans and animals: the turnover rate of platelets is accelerated; the uptake of serotonin by platelets is reduced; the metabolism of serotonin by the endothelial cells is decreased; the vascular smooth muscles are hyperresponsive to the constrictor effects of serotonin and other serotonergic agonists; the S2-serotonergic antagonist ketanserin, which is devoid of agonistic properties, lowers arterial blood pressure in hypertensive humans. Whether the alpha-adrenergic blocking properties of ketanserin contribute to its antihypertensive properties in humans is still a matter of discussion.