Centrally mediated antihypertensive and bradycardic effects of methysergide in spontaneously hypertensive rats.

Methysergide caused dose-dependent reductions in systolic blood pressure and heart rate of unanesthetized SHR, whereas cyproheptadine was ineffective. In pithed SHR pretreated with methysergide or cyproheptadine, pressor responses to 5-HT were abolished. Responses to sympathetic nerve stimulation were unaltered by methysergide, whereas cyproheptadine slightly reduced them. Both drugs enhanced pressor responses to norepinephrine. Failure to identify a peripheral mechanism for the antihypertensive action of methysergide suggests that the effect may be centrally mediated but not reliant upon serotonin receptor blockade.