ANTI-FREE RADICAL MECHANISMS IN CAPTOPRIL PROTECTION AGAINST REPERFUSION INJURY IN ISOLATED RAT HEARTS

OBJECTIVE: Captopril, an angiotensin-converting enzyme (ACE) inhibitor , is known to modulate ischemia-reperfusion injury in the isolated hea rts. This study was designed to examine the involvement of anti-free r adical mechanisms in this protection. METHODS: Isolated perfused rat h earts were subjected to 60 mins of global ischemia and 30 mins of repe rfusion with or without captopril (100 mu mol/L). Myocardial resting t ension and contractile force were recorded. At the end of reperfusion, hearts were analyzed for the activities of antioxidant enzymes, super oxide dismutase, glutathione peroxidase and catalase, as well as for t he extent of lipid peroxidation. Another potent ACE inhibitor, enalapr il (100 mu mol/L) was used for comparison. RESULTS: Captopril signific antly improved the recovery of con tractile function as well as attenu ated the rise in resting tension in the ischemic-reperfused hearts as compared to the control Captopril-exposed ischemic-reperfused hearts s howed an increase in the activity of superoxide dismutase with no chan ge in glutathione peroxidase and catalase enzyme activities. Lipid per oxidation at the end of reperfusion was significantly attenuated in th e captopril-exposed hearts compared to the control. Enalapril had no p rotective effect against ischemia-reperfusion induced contractile fail ure or rise in resting force. CONCLUSIONS: These results suggest that cardioprotection by captopril against ischemia-reperfusion injury, may involve an anti-free radical mechanism independent of its ACE inhibit ion property.