The effect of angiotensin-converting enzyme inhibitors on human neutrophil chemotaxis in vitro.
1. Myocardial 'reperfusion injury' has been partly attributed to the production of free radicals which are cytotoxic towards cells. Neutrophils are recruited by ischaemic tissue and are one source of free radicals. Angiotensin-converting enzyme (ACE) inhibitors can reduce 'reperfusion injury' and we decided to determine if ACE inhibitors might contribute to this effect by inhibiting neutrophil chemotaxis. 2. The effects of captopril (a thiol containing ACE inhibitor) and enalaprilat (a nonthiol ACE inhibitor) and N-mercaptopropionyl glycine (MPG) (a simple thiol) on neutrophil chemotaxis were tested in an in vitro Boyden chamber assay. 3. The chemotactic response of human neutrophils to fMLP was reduced by 27.6% with MPG (n = 8; P < 0.05), by 13.2% with enalaprilat (n = 8; P = 0.075) and by 5.2% with captopril (n = 8; P = 0.66) at 5 microM (therapeutic concentration.) 4. Neutrophil chemotaxis was significantly decreased with 50 microM and 500 microM MPG and enalaprilat and 500 microM captopril. 5. Supratherapeutic concentrations of ACE inhibitors can reduce neutrophil chemotaxis at high concentrations and this effect does not appear to be -SH dependent.
Clapperton
M
M
Department of Cardiology, Western Infirmary, Glasgow.
McMurray
J
J
Fisher
A C
AC
Dargie
H J
HJ
D002216:Captopril / Q000494:pharmacology*; D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015773:Enalaprilat / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D008625:Tiopronin / Q000494:pharmacology*
D009240:N-Formylmethionine Leucyl-Phenylalanine; D002216:Captopril; D008625:Tiopronin; D015773:Enalaprilat