Involvement of Estrogen Receptor and Mitochondrial KATP Channels in Cardioprotective Effect of Remote Aortic Preconditioning in Isolated Rat Heart

Abstract

The present study was designed to investigate the role of estrogen receptor and KATP channel in cardioprotective effect of remote aortic preconditioning in rat heart. Remote preconditioning is a phenomenon in which brief episodes of ischemia and reperfusion to remote organs protect the target organ against sustained ischemia/ reperfusion induced injury. Protective effects of remote aortic preconditioning are well established in the heart, but their mechanisms still remain to be elucidated. Remote aortic preconditioning in rats was produced by introducing four episodes of ischemia and reperfusion, each comprising of 5 min occlusion and 5 min reperfusion, through abdominal aorta. Perfused rat heart was isolated and subjected to global ischemia for 30 min followed by reperfusion for 120 min. The degree of cardiac injury was assessed by analysing the level of lactate dehydrogenase, creatin kinase, reactive oxygen species and nitrite in coronary effluent. Myocardial infarct size was also estimated macroscopically using tetrazolium tri chloride staining. Ethylinestradiol (10 μg/kg, orally) as estrogen receptor agonist was noted to reproduce remote aortic preconditioning mediated cardioprotection in ovariectomized rat. However, administration of glibenclamide along with or prior to ethylinestradiol abolished cardioprotection. Moreover, glibenclamide a KATP channel blocker, abolish cardioprotective effect of remote aortic preconditioning with daidzein a caveolin inhibitor (0.2 mg/kg subcutaneous). Ethylinestradiol significantly increased the release of nitric oxide and restored the attenuated cardioprotective effect of remote aortic preconditioning. These data provide the evidence that estrogen receptor activation involved in cardioprotective effect of remote aortic preconditioning-mediated trough opening of KATP channels.