| Abstract: | The protection of angiotensin converting enzyme (ACE) inhibitors, captopril and ramiprilat, against free radical-mediated myocardial injury were studied in isolated working rat hearts. Free radicals were generated by electrolysis of Krebs-Henseleit solution with 10 mA direct current for 1 min. Both captopril (360 μmol/l) and ramiprilat (12.5 μmol/l) significantly reduced the decrease of left ventricle dP/dt′max, coronary flow (CF), myocardial superoxide dismutase (SOD) and creatine kinase (CK) activities and the elevation of S-T segment of epicardial ECG as well as the rise of myocardial malondialdehyde (MDA) content caused by electrolysed perfusate. Captopril afforded a dose-dependent protection on cardiac functions with various concentrations of 45, 90, 180 and 360 μmol/l. Iloprost (30 nmol/l), a stable mimetic of prostacyclin, could also alleviate free radical-mediated myocardial injuries. All the beneficial effects of ramiprilat (12.5 μmol/l) were abolished by the administration of indomethacin (5 μmol). In contrast, captopril (90 μmol/l) still exhibited significant protective effects after indomethacin (9 μmol) was administered, though these protective effects were insignificantly weakened. In order to assess the role of sulfhydryl (-SH) group in the effects of captopril, a SH-containing drug S8 and a disulfide DG4, both are deficient in ACE inhibitory properties in vitro, were examined. Data showed that S8 (180 μmol/l) provided a significant protection while DG4 showed no protective effect. It is concluded that ACE inhibitors can protect against free radical-induced myocardial damage. Ramiprilat, a non-SH-containing ACE inhibitor, inhibits free radical-induced damages mainly by stimulation of prostacyclin synthesis and/or release. In addition to this effect, captopril, a SH-containing ACE inhibitor, may exert additional anti-free radical effects by a mechanism which is probably related to the sulfhydryl group. |
