Alpha blocking action of the antihypertensive agent, prazosin

The vasodilatory and alpha adrenergic blocking properties of prazosin were studied in anesthetized rats and compared with the direct-acting vasodilator, diazoside. The hypotensive activity of diazoxide was unimpaired after ganglion blockade with pentolinium or alpha adrenoreceptor blockade with phentolamine; diazoxide also significantly attenuated angiotensin II pressor responses. In contrast, the hypotensive action of prazosin was completely abolished, over a 10(4)-fold dose range, after ganglion or alpha adrenoreceptor blockade, and this agent failed, even in maximal hypotensive doses, to attenuate angiotensin II pressor responses. In addition, prazosin was shown to possess potent alpha adrenoreceptor blocking properties, significantly attenuating norepinephrine pressor responses and causing reversal of epinephrine pressor responses. These studies in the rat indicate that the hypotensive action of prazosin is not due to a direct relaxant effect upon vascular smooth muscle, but is attributable to alpha adrenoreceptor blockade.