Bradykinin-potentiating activity of captopril disulphide dimer (SQ 14,551).
The ability of captopril and one of its metabolites, the disulphide dimer have been studied for their ability to affect angiotensin I and bradykinin responses. Captopril disulphide dimer (i.v.) potentiated the vasodilatory effects of bradykinin in urethane-anaesthetized rats, at doses of 0.1 and 0.3 mg/kg but did not inhibit the angiotensin I-mediated pressor response at these same concentrations. This activity of captopril disulphide dimer in vivo was not seen with bradykinin responses in isolated guinea pig ileum except at bath concentrations much higher than for captopril (10(-5) M). However captopril and captopril disulphide dimer at oral doses of 10 mg/kg both lowered systolic and diastolic blood pressures in spontaneously hypertensive rats. These studies are consistent with an in vivo bradykinin-potentiating activity of captopril disulphide dimer and suggest a possible antihypertensive activity of disulphide metabolites of captopril.
Drummer
O H
OH
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Kourtis
S
S
D000758:Anesthesia; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004357:Drug Synergism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013997:Time Factors
D000803:Angiotensin I; D002216:Captopril; D001920:Bradykinin; C035974:captopril disulfide