Possible mechanism of cardioprotective effect of angiotensin preconditioning in isolated rat heart.
The present study is designed to investigate the mechanism of cardioprotective effect of angiotensin II preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for lactate dehydrogenase and creatine kinase enzyme release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using triphenyltetrazolium chloride staining. Four episodes of angiotensin II preconditioning markedly reduced lactate dehydrogenase and creatine kinase release in the coronary effluent and decreased myocardial infarct size. Administration of prazosin (alpha(1)-adrenoceptor antagonist) before global ischaemia reduced the extent of ischaemia-reperfusion-induced myocardial injury. Moreover, administration of prazosin during angiotensin II preconditioning or depletion of biogenic amines by reserpinisation (0.5 mg/kg i.p.) did not affect the cardioprotective effect of angiotensin II preconditioning. On the other hand, colchicine (5 mg/kg i.p.) or polymyxin B (50 microM) treatment markedly attenuated the cardioprotective effect of angiotensin II preconditioning. On the basis of these results, it may be concluded that the cardioprotective effects of angiotensin II preconditioning may be mediated through protein kinase C and may not involve release of norepinephrine or activation of alpha(1)-adrenoceptor.
Sharma
A
A
Department of Pharmaceutical Sciences & Drug Research, Punjabi University, 147002, Patiala, India.
Singh
M
M
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003078:Colchicine / Q000494:pharmacology; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D011113:Polymyxins / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D002317:Cardiovascular Agents; D011113:Polymyxins; D000804:Angiotensin II; D012110:Reserpine; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D003078:Colchicine; D014439:Tyramine; D011224:Prazosin