Evaluation of the ability of the angiotensin-converting enzyme inhibitor captopril to scavenge reactive oxygen species.

Captopril, an inhibitor of angiotensin-converting enzyme, has been suggested to have additional cardioprotective action because of its ability to act as an antioxidant. 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 less than 10(3) M-1 s-1) or hydrogen peroxide (rate constant less than M-1 s-1). It does not inhibit peroxidation of lipids stimulated by iron ions and ascorbate or by the myoglobin/H2O2 system. Indeed, mixtures of ferric ion and captopril can stimulate lipid peroxidation. Captopril reacts rapidly with hydroxyl radical (rate constant greater than 10(9) M-1 s-1) but might be unlikely to compete with most biological molecules for OH because of the low concentration of captopril 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 alpha 1-antiproteinase (alpha 1 AP) against inactivation 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.