Captopril and enalaprilat do not scavenge the superoxide anion.
The ability of captopril and enalaprilat, 2 angiotensin-converting enzyme (ACE) inhibitors, to scavenge superoxide anion radical was examined. With use of a number of superoxide-generating systems, such as xanthine-xanthine oxidase, phorbol myristate acetate-activated neutrophils, auto-oxidizing dihydroxyfumarate, and auto-oxidation of epinephrine to adrenochrome, captopril was seen not to scavenge superoxide directly, because it did not inhibit superoxide-dependent cytochrome c or nitro-blue tetrazolium reduction. Superoxide-dependent cytochrome c reduction was inhibited only when captopril was preincubated with a lower concentration of cytochrome c (22 microM). This effect was due to a decrease in the concentration of cytochrome c, because captopril reduced cytochrome c directly. When this effect was compensated for, no cytochrome c reduction induced by superoxide was observed. Captopril inhibited the auto-oxidation of epinephrine to adrenochrome at pH 10.2 where this auto-oxidation is superoxide-dependent, and at pH 7.8 where it is superoxide-independent and superoxide dismutase insensitive. It appears that captopril, in this respect, acted as a nonspecific antioxidant, probably by reducing an intermediate in the complex oxidation of epinephrine to adrenochrome. Therefore, caution may be used in interpreting the role of captopril in the attenuation of reperfusion-induced myocardial dysfunction and in attributing this effect to the inhibition of free radical mechanism.
Kukreja
R C
RC
Department of Medicine, Medical College of Virginia, Richmond 23298.
Kontos
H A
HA
Hess
M L
ML
D002216:Captopril / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D015773:Enalaprilat / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism; D005650:Fumarates / Q000378:metabolism; D006801:Humans; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*
D003574:Cytochrome c Group; D005650:Fumarates; D013481:Superoxides; C005998:dihydroxyfumarate; D009580:Nitroblue Tetrazolium; D002216:Captopril; D015773:Enalaprilat; D004837:Epinephrine