Studies on the mechanism of captopril induced hypotension in rats.
The mechanism of the hypotensive response to captopril was investigated in pithed and urethane anesthetized rats. Cumulative intravenous doses of captopril produced dose-dependent hypotensive responses which were correlated with blockade of the pressor response to angiotensin I. Angiotensin II responses were unaffected. Infusions of saralasin, an angiotensin receptor antagonist, inhibited the hypotensive action of captopril, the degree of antagonism being correlated with inhibition of angiotensin II pressor responses. Bilateral nephrectomy lowered blood pressure to approximately the same level as captopril and completely abolished the hypotensive effect of captopril. No evidence was obtained for the involvement of endogenous bradykinin or prostaglandins in the hypotensive action of captopril. It is concluded that in pithed and urethane anesthetized rats, captopril mediates its hypotensive response by removing the renal renin-angiotensin system, most probably via inhibition of angiotensin I - converting enzyme. The results contrast with similar studies conducted in anesthetized dogs. In this species, the mechanism of action of captopril remains for further resolution.
D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000502:physiology; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007022:Hypotension / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D012504:Saralasin / Q000494:pharmacology
D000809:Angiotensins; D000803:Angiotensin I; D011392:Proline; D002216:Captopril; D012504:Saralasin; D001920:Bradykinin; D007213:Indomethacin