PRESSER RESPONSES TO THE ALPHA(1)-ADRENOCEPTOR AGONIST CIRAZOLINE - EFFECTS OF CAPTOPRIL, PHENOXYBENZAMINE AND NIFEDIPINE

We have examined the effects of captopril on presser responses to the selective alpha(1)-adrenoceptor agonist cirazoline in the pithed rat p reparation following treatment with phenoxybenzamine and/or nifedipine . Pretreatment with captopril reduced the presser responses to cirazol ine and displaced the dose-response curve for this agonist to the righ t, significantly increasing the ED(50) without altering the maximum re sponse. Pretreatment with phenoxybenzamine accentuated the inhibitory actions of captopril and a combination of phenoxybenzamine and captopr il significantly increased the ED(50) without altering the maximum res ponse. Administration of nifedipine in animals, which had already rece ived phenoxybenzamine and captopril, led to a further displacement to the right of the cirazoline dose-response curve. The ED(50) was found to be significantly increased and the maximum response was now signifi cantly depressed. Captopril produced further additive inhibition with nifedipine and phenoxybenzamine of the vasoconstrictor effects of cira zoline. These data indicate, perhaps not surprisingly, that the cellul ar basis for the inhibitory effects of captopril is different from tha t of nifedipine and phenoxybenzamine, however, more importantly, that captopril may directly, or indirectly, inhibit receptor-operated catio n channel mediated presser responses.