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 hearts. This study was designed to examine the involvement of anti-free radical mechanisms in this protection.


METHODS
Isolated perfused rat hearts were subjected to 60 mins of global ischemia and 30 mins of reperfusion with or without captopril (100 mumol/L). Myocardial resting tension and contractile force were recorded. At the end of reperfusion, hearts were analyzed for the activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase, as well as for the extent of lipid peroxidation. Another potent ACE inhibitor, enalapril (100 mumol/L) was used for comparison.


RESULTS
Captopril significantly improved the recovery of contractile function as well as attenuated the rise in resting tension in the ischemic-reperfused hearts as compared to the control. Captopril-exposed ischemic-reperfused hearts showed an increase in the activity of superoxide dismutase with no change in glutathione peroxidase and catalase enzyme activities. Lipid peroxidation at the end of reperfusion was significantly attenuated in the captopril-exposed hearts compared to the control. Enalapril had no protective effect against ischemia-reperfusion induced contractile failure 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 inhibition property.
Anderson
B
B
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Manitoba.
Khaper
N
N
Dhalla
A K
AK
Singal
P K
PK
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D005609:Free Radicals; D004656:Enalapril; D002216:Captopril; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase