BACKGROUND: Reactive oxygen free radicals have been implicated as an important factor in the development of ischemia-reperfusion injury of heart. Captopril, a SH-containing angiotensin converting enzyme(ACE) inhibitor has been reported to provide the protective effect in different models of myocardial ischemia and reperfusion injury of animal hearts. It is postulated that the myocardial protective effect may be related to a potential anti-free radical effect independent of ACE inhibition. The present study was designed to elucidate the myocardial protective mechanism of Captopril by investigating the drug effect on the experimentally induced oxygen free radical-mediated myocardial injury in isolated hearts of rats. METHODS: The heart isolated from rat was perfused retrogradly by Langendorff method. Myocardial dysfuntion was induced by oxygen free radicals generated by electrolysis of the perfusing solution(Kreb-Henseleit) with 2mA direct current for 45 sec. The cardiac functions(left ventricular pressure, dP/dt, heart rate, coronary flow) and the ventricular content of a lipid peroxidation product, malondialdehyde(MDA) were measured under presence of absence of Captopril and the compairing drugs(enalaprilat, cysteine and dithiothreitol). RESULTS: Electrolysis of oxygen-saturated Krebs-Henseleit perfusing solution led to the production of superoxide anion increasingly with intensity and duration of the applied electric current. The hearts perfused with the electroyzed solution demonstrated significant decrease in left ventricular pressure, dp/dt, heart rate, coronary folw and increase in myocardial MDA content. The depression of myocardial function as well as the increase of MDA content and oxygen radical production were reversed by Captopril(0.75~2mM) dose-dependently. Enalaprilat, a non-SH containing ACE inhibitor, however, showed no protective effect at all. Cysteine and dithiothreitol, the SH-containing agents without ACE inhibitory action showed also protective effects on the myocardial depression induced by electrolysis. CONCLUSION: It is suggested that Captopril may exert protective effect on oxygen radical-mediaed myocardial injury probably by its antioxidative and anti-free radical mechanism related to SH-group.
Angiotensins ; Animals ; Captopril* ; Cysteine ; Depression ; Dithiothreitol ; Electrolysis ; Enalaprilat ; Free Radicals ; Heart ; Heart Rate ; Lipid Peroxidation ; Myocardial Ischemia ; Oxygen ; Rats ; Reperfusion Injury ; Superoxides ; Ventricular Pressure