MECHANISM OF HYPOTENSIVE ACTION OF PRAZOSIN

Abstract

The mechanism of action of prazosin was studied in anesthetized rats by comparison with peripherally-acting antihypertensive agents, indoramin, hydralazine and diazoxide. Hydralazine and diazoxide retained full hypotensive potency after ganglionic blockade with pentolinium or .alpha.-adrenoceptor blockade with phentolamine. Hydralazine and diazoxide attenuated angiotensin II pressor responses. The hypotensive activity of prazosin was completely abolished and that of indoramin was almost abolished by pentolinium or phentolamine pre-treatment. Neither prazosin nor indoramin caused impairment of angiotensin II responsivity, but each was shown to possess .alpha.-adrenoceptor blocking properties. Both agents antagonized pressor action of norepinephrine and reversed responses to epinephrine. While hydralazine and diazoxide act directly upon the vasculature by mechanisms independent of sympathetic vasomotor tone, prazosin, like indoramin, acts as an .alpha.-adrenoceptor blocking agent.