Cardioprotective effect of zofenopril in perfused rat heart subjected to ischemia and reperfusion.
We investigated the effect of different ACE inhibitors on tissue injury in isolated rat hearts subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Zofenoprilat (1-100 microM), but not enalaprilat or lisinopril, significantly reduced infarct size, as estimated on the basis of triphenyltetrazolium chloride staining. The protection was not reproduced by the angiotensin II receptor antagonist irbesartan, and it was partly abolished by the bradykinin receptor antagonist HOE 140. Zofenoprilat molecule contains a sulfhydryl group, and its administration, as compared with enalaprilat or lisinopril administration, was associated with better preservation of protein thiols at the end of ischemia. We conclude that zofenopril has a specific cardioprotective effect, which might be related either to interference with bradykinin metabolism or to preservation of protein sulfhydryl groups.
Frascarelli
Sabina
S
Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Pisa, Italy.
Ghelardoni
Sandra
S
Ronca-Testoni
Simonetta
S
Zucchi
Riccardo
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; C044958:zofenopril; D002216:Captopril