Captopril and quinapril reduce reactive oxygen species.
BACKGROUND
Angiotensin-converting enzyme inhibitors may affect reactive oxygen species in humans in vitro and in vivo. In the present study we evaluated whether angiotensin-converting enzyme inhibitors may affect NAD(P)H oxidase activity.


METHODS
The production of reactive oxygen species was measured spectrophotometrically in mononuclear leukocytes using the fluorescent dye, dichlorofluorescein diacetate. The effects of quinaprilat, captopril, enalaprilat and lisinopril on phorbol myristate acetate-induced reactive oxygen species generation were investigated in vitro. The effects of quinaprilat, captopril, enalaprilat and lisinopril on the NAD(P)H oxidase activity of the mononuclear leukocytes were measured photometrically. In addition, reactive oxygen species were measured before and 4 h after oral administration of quinapril.


RESULTS
In vitro, the addition of quinaprilat (72 +/- 6% of control; mean +/- SEM; n= 19; P < 0.001) and captopril (48 +/- 2% of control; n= 19; P < 0.001) significantly reduced the phorbol-12-myristate-13-acetate-induced reactive oxygen species generation by the mononuclear leukocytes, whereas enalaprilat and lisinopril showed no effect. The effect of captopril on phorbol-12-myristate-13-acetate-induced reactive oxygen species generation in vitro was concentration-dependent. Quinaprilat and captopril significantly inhibited the NAD(P)H oxidase activity. After the oral administration of 10 mg of quinapril the phorbol-12-myristate-13-acetate-induced reactive oxygen species generation by the mononuclear leukocytes was significantly decreased from 1981 +/- 292% to 988 +/- 141% (n = 14; P < 0.01).


CONCLUSIONS
Quinapril and captopril decrease the production of reactive oxygen species.
van der Giet
M
M
University-Klinik Benjamin-Franklin, FU-Berlin, Berlin, Germany.
Erinola
M
M
Zidek
W
W
Tepel
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D017706:Lisinopril / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D000077583:Quinapril; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007546:Isoquinolines; D017382:Reactive Oxygen Species; D044005:Tetrahydroisoquinolines; C037631:2',7'-dichlorofluorescein; D002216:Captopril; D017706:Lisinopril; D019255:NADPH Oxidases; D015773:Enalaprilat; D013755:Tetradecanoylphorbol Acetate; D000077583:Quinapril