Mechanism of the depressor effect of bromocriptine in the spontaneously hypertensive rat

S Nagahama, YF Chen and S Oparil

Bromocriptine, a dopamine (DA) agonist which passes the bloodbrain barrier, has been shown to have a depressor effect in the spontaneously hypertensive rat of the Okamoto strain. To elucidate the mechanism of this depressor effect, the responses of mean arterial blood pressure and plasma epinephrine (EP), norepinephrine, prolactin and renin activity to i.v. administration of bromocriptine (500 micrograms/kg), alone and after pretreatment with i.v. metoclopramide, a DA antagonist which crosses the blood-brain barrier, and domperidone, a DA antagonist which does not cross the blood-brain barrier, were examined in conscious unrestrained spontaneously hypertensive rats. Metoclopramide attenuated the depressor action of bromocriptine in a dose-related manner, but domperidone had no effect. Neither metoclopramide nor domperidone given alone altered mean arterial blood pressure. Bromocriptine given alone decreased plasma prolactin and increased plasma EP without altering plasma norepinephrine or plasma renin activity. Pretreatment with either metoclopramide or domperidone completely blocked the EP-stimulating effects of bromocriptine. Neither DA antagonist given alone had an effect on plasma EP, norepinephrine or plasma renin activity; both agents stimulated prolactin release. These results suggest that the depressor action of i.v. administered bromocriptine is mediated mainly through a central dopaminergic mechanism rather than by peripheral effects and that plasma EP responses to bromocriptine do not directly contribute to its depressor action.

Volume 228, Issue 2, pp. 370-375, 02/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

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