THE EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS ON HUMAN NEUTROPHIL CHEMOTAXIS IN-VITRO

1 Myocardial 'reperfusion injury' has been partly attributed to the pr oduction of free radicals which are cytotoxic towards cells. Neutrophi ls are recruited by ischaemic tissue and are one source of free radica ls. Angiorensin-converting enzyme (ACE) inhibitors can reduce 'reperfu sion injury' and we decided to determine if ACE inhibitors might contr ibute to this effect by inhibiting neutrophil chemotaxis. 2 The effect s of captopril (a thiol containing ACE inhibitor) and enalaprilat (a n onthiol ACE inhibitor) and N-mercaptopropionyl glycine (MPG) (a simple thiol) on neutrophil chemotaxis were tested in an in vitro Boyden cha mber assay. 3 The chemotactic response of human neutrophils to fMLP wa s reduced by 27.6% with MPG (n = 8; P < 0.05), by 13.2% with enalapril at (n = 8; P = 0.075) and by 5.2% with captopril (M = 8; P = 0.66) at 5 mu M (therapeutic concentration.) 4 Neutrophil chemotaxis was signif icantly decreased with 50 mu M and 500 mu M MPG and enalaprilat and 50 0 CIM captopril. 5 Supratherapeutic concentrations of ACE inhibitors c an reduce neutrophil chemotaxis at high concentrations and this effect does not appear to be -SH dependent.