EFFECTS OF SULFHYDRYL-CONTAINING AND NON-SULFHYDRYL-CONTAINING ACE-INHIBITORS ON LEFT-VENTRICULAR RELAXATION IN THE ISOLATED GUINEA-PIG HEART

ACE inhibitors exert both acute and chromic beneficial effects on card iac function (e.g remodelling, diastolic dysfunction). We have previou sly reported that the ACE inhibitor captopril induces selective left v entricular (LV) relaxant effects in the isolated ejecting guinea pig h eart. The aim of the present study was to further investigate the mech anism of the captopril-induced changes in early LV relaxation by compa ring the effects of two sulphydryl and two non-sulphydryl containing A CE inhibitors in the same experimental preparation. Isolated ejecting guinea pig hearts were studied under conditions of constant loading an d heart rate. LV pressure was monitored by a 2F micromanometer-tipped catheter transducer inserted in the LV cavity. The sulphydryl-containi ng ACE inhibitors captopril and zofenaprilat enhanced early LV relaxat ion, whereas the non-sulphydryl-containing ACE inhibitors lisinopril a nd quinaprilat did not. The effects of captopril and zofenaprilat were attenuated both by the nitric oxide-scavenger haemoglobin and the bra dykinin B-2-kinin receptor antagonist HOE 140. Neither the oxygen free -radical scavenger superoxide dismutase nor the sulphydryl-containing compound N-acetyl cysteine administered together with lisinopril had a ny effect on LV relaxation, These data demonstrate that inhibition of intra-cardiac ACE activity may acutely modulate LV relaxation through increased activity of the bradykinin-nitric oxide pathway. The presenc e of a sulphydryl group on the relevant ACE inhibitor appears to be es sential for this LV relaxant effect.