Analysis of the mechanism of acute decrease of blood pressure induced by captopril (SQ 14,225) in dogs by the use of aprotinin, SAR1-ILE8-angiotensin II and indomethacin.

Acute effects of captopril (SQ 14 225) on blood pressure were investigated in pentobarbital anesthetized dogs. Intravenous captopril (0.1-3 mg/kg) caused reduction of blood pressure dose-independently, while dose-dependent attenuation of exogenous angiotensin I-induced pressor response and potentiation of bradykinin-induced reduction of blood pressure were observed wih the same doses of this agent. This acute decrease in blood pressure was partially inhibited by a pretreatment with any one of aprotinin, Sar1-Ile-8-angiotensin II and indomethacin. More significant inhibition of the blood pressure decrease was observed after the combined pretreatment with Sar1-Ile8-angiotensin II and indomethacin or that with all the three drugs, though no complete abolition of the blood pressure decrease was achieved. These results suggest that captopril may decrease blood pressure in anesthetized dogs through other mechanism(s) in addition to angiotensin converting enzyme inhibition, including the prostaglandin release probably from the kidney.