Converting enzyme inhibition and modulation of plasma renin activity with captopril in anesthetized rats.
We examined the effects of an orally active inhibitor of converting enzyme, captopril (D-3-mercapto-2-methylpropanoyl-L-proline), in pentobarbital-anesthetized rats. Intravenous (i.v.) administration of captopril (0.1, 0.3, 1.0, 3.0 mg/kg) resulted in a dose-dependent inhibition of the pressor responses to angiotensin I (1.0 micrograms/kg, i.v.); at 1.0 mg/kg, captopril markedly potentiated the magnitude and duration of vasodepressor responses elicited by bradykinin (0.3 micrograms/kg, i.v.). Captopril effected a marked elevation of plasma renin activity by its blocking action on the angiotensin II-mediated negative feedback of renin release without markedly altering systemic blood pressure and heart rate. Propranolol (1.5 mg/kg, i.v.), at a dose which almost completely inhibited isoproterenol (0.15 micrograms/kg/min, i.a.)-induced renin release, tended to suppress the captopril-induced renin release. However, indomethacin (5.0 mg/kg, i.v.) failed to change the captopril-induced renin release. These findings suggest that captopril specifically inhibits converting enzyme and kininase II, and that captopril-induced renin release is partially associated with the beta-adrenergic system without dedication by prostaglandins.
D000109:Acetylcholine / Q000494:pharmacology; D000758:Anesthesia; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D011392:Proline; D002216:Captopril; D012083:Renin; D007545:Isoproterenol; D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine