Effect of captopril, enalaprilat and mercaptopropionyl glycine (MPG) on the oxidative activity of human isolated neutrophils.
1. Neutrophil NADPH oxidase produces the superoxide anion (O2-) anion 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 ability of this drug to alleviate neutrophil-mediated tissue damage. We have, therefore, investigated the effect of captopril on the oxidative activity of intact human isolated neutrophils. 2. The effects of captopril on neutrophil oxidative activity were compared with those of enalaprilat (a non-thiol ACE inhibitor) and N-mercaptopropionyl glycine (MPG) (a simple thiol). 3. The oxidative response of PMA-stimulated neutrophils measured by lucigenin chemiluminescence was not affected by any of these test agents. The thiol captopril and MPG (but not enalaprilat) caused an initial delay in luminol chemiluminescence production by PMA-stimulated neutrophils. 4. Captopril and MPG (but not enalaprilat) increased, rather than decreased oxygen uptake, when added to PMA-stimulated neutrophils. Thiol oxidation was determined to be, at least partly, 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 contribute to the therapeutic effects of captopril and other thiols.
Clapperton
M
M
Bioengineering Unit, Strathclyde University, Glasgow, Scotland.
Beswick
P H
PH
Abdullah
I
I
Dargie
H J
HJ
Fisher
A C
AC
McMurray
J
J
D000166:Acridines / Q000737:chemistry; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D008625:Tiopronin / Q000494:pharmacology
D000166:Acridines; D000806:Angiotensin-Converting Enzyme Inhibitors; D013481:Superoxides; C033472:10,10'-dimethyl-9,9'-biacridinium; D002216:Captopril; D008625:Tiopronin; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D015773:Enalaprilat