EFFECT OF CAPTOPRIL, ENALAPRILAT AND MERCAPTOPROPIONYL GLYCINE (MPG) ON THE OXIDATIVE ACTIVITY OF HUMAN ISOLATED NEUTROPHILS

1 Neutrophil NADPH oxidase produces the superoxide anion (O-2(.-)) ani on radical from oxygen. The thiol containing ACE inhibitor, captopril has been reported to inhibit isolated NADPH oxidase. The above effect of captopril, if present in intact cells, could contribute to the abil ity of this drug to alleviate neutrophil-mediated tissue damage. We ha ve, therefore, investigated the effect of captopril on the oxidative a ctivity of intact human isolated neutrophils. 2 The effects of captopr il on neutrophil oxidative activity were compared with those of enalap rilat (a non-thiol ACE inhibitor) and N-mercaptopropionyl glycine (MPG ) (a simple thiol). 3 The oxidative response of PMA-stimulated neutrop hils measured by lucigenin chemiluminescence was not affected by any o f these test agents. The thiols captopril and MPG (but not enalaprilat ) caused an initial delay in luminol chemiluminescence production by P MA-stimulated neutrophils. 4 Captopril and MPG (but not enalaprilat) i ncreased, rather than decreased oxygen uptake, when added to PMA-stimu lated neutrophils. Thiol oxidation was determined to be, at least part ly, responsible for the excess oxygen uptake observed. 5 NADPH oxidase activity in intact neutrophils was not affected by captopril, MPG or enalaprilat. The inhibition of NADPH oxidase activity is unlikely to c ontribute to the therapeutic effects of captopril and other thiols.