Mechanism of the hypotensive action of prazosin

The mechanism of action of prazosin was studied in anesthetized rats by comparison with the peripherally-acting anti-hypertensive agents, indoramin, hydralazine and diazoxide. Hydralazine and diazoxide retained full hypotensive potency after ganglionic blockade with pentolinium or alpha adrenoceptor blockade with phentolamine. Hydralzaine and diazoxide also attenuated angiotensin II pressor responses. In contrast, the hypotensive activity of prazosin was completely abolished, and that of indoramin was almost abolished by either 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 the pressor action of norepinephrine and reversed responses to epinephrine. Thus, 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.