Serotonin released from aggregating platelets can reach sufficient concentrations to affect local vascular function in a number of ways. The monoamine can cause contraction of blood vessels by its direct action on smooth muscle or by potentiating the effect of other vasoconstrictor agents. It can also induce vasodilatation by a direct relaxing effect on smooth muscle, by inhibition of adrenergic nerves, and by release of an uncharacterised relaxing factor from endothelial cells. One of its most likely physiological roles is to aid in haemostasis by promoting platelet aggregation and by causing local vasoconstriction at sites of injury. It probably has a role in some forms of vascular pathology as well: it may contribute to vasospasm of cerebral, coronary, and digital arteries, particularly if there is endothelial dysfunction or damage.
Much evidence has implicated serotonin (5-hydroxytryptamine) in the pathogenesis of migraine. Serotonergic agonists, such as ergotamine, and antagonists, such as methys-ergide and pizotifen, are both used in therapy of migraine. Promising but conflicting early results have not yet defined a place for serotonergic antagonists in other vasospastic disorders. The antihypertensive efficacy of one serotonergic antagonist, ketanserin, raises questions about the possible involvement of serotonin in either the initiation or the maintenance of the elevated peripheral vascular resistance in several forms of hypertension, including essential hypertension.