Chem -Bwl. Interactwns, 77 (1991) 303--314 303 Elsevier Scientific Publishers Ireland Ltd. EVALUATION OF THE ABILITY OF THE ANGIOTENSIN-CONVERTING ENZYME INHIBITOR CAPTOPRIL TO SCAVENGE REACTIVE OXYGEN SPECIES OKEZIE I. ARUOMA a, DOLA AKANMU ~, RUBENS CECCHINIa,* and BARRY HALLIWELLb aDepartment of Biochemistry, University of London King's College, Strand Campus, London WC~R ~LS (U.K.) and aDivision of Pulmonary-Cmtical Care Medw~ne, UC Davis Medical Center, Professional Building, 4301 X St., Sacramento, CA 95817 (U.S.A.) (Received September 27th, 1990) (Revision received October 29th, 1990) (Accepted November 1st, 1990) SUMMARY Captopril, an inhibitor of angiotensin-converting enzyme, has been suggested to have additional cardioprotective action because of its ability to act as an an- tioxidant. The rates of reaction of captopril with several biologically-relevant reactive oxygen species were determined. Captopril reacts slowly, if at all, with superoxide (rate constant < 108 M -1 s -1) or hydrogen peroxide (rate constant < 1 M-~ s-l). It does not inhibit peroxidation of lipids stimulated by iron ions and ascorbate or by the myoglobin]H202 system. Indeed, mixtures of ferric ion and captopril can stimulate lipid peroxidation. Captopril reacts rapidly with hydroxyl radical (rate constant > 109 M -1 s -1) but might be unlikely to compete with most biological molecules for "OH because of the low concentration of cap- topril that can be achieved in vivo during therapeutic use. Captopril did not significantly inhibit iron ion-dependent generation of hydroxyl radicals from hydrogen peroxide. By contrast, captopril is a powerful scavenger of hypochlorous acid: it was able to protect %-antiproteinase (%AP) against inac- tivation by this species and to prevent formation of chloramines from taurine. We suggest that the antioxidant action of captopril in vivo is likely to be limited, and may be restricted to protection against damage by hypochlorous acid derived from the action of neutrophil myeloperoxidase. Key words: Captopril -- Antioxidant -- Reperfusion injury -- Hydroxyl radical -- Superoxide -- Hypochlorous acid Correspondence to: O.I. Aruoma, Department of Biochemistry, University of London King's College, Strand Campus, London WC2R 2LS, U.K. *Present address: Dept of General Pathology, University of Londrina, Londrina PR, Brazil. 0009-2797/91/$03.50 © 1991 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland