Signal mechanism activated by erythropoietin preconditioning and remote renal preconditioning-induced cardioprotection

It has been recently reported that release of erythropoietin could mediate the cardioprotective effects of remote renal preconditioning. However, the mechanism of erythropoietin-mediated cardioprotection in remote preconditioning is still unexplored. Therefore, the present study was designed to investigate the possible signal transduction pathway of erythropoietin-mediated cardioprotection in remote preconditioning in rats. Remote renal preconditioning was performed by four episodes of 5 min renal artery occlusion followed by 5 min reperfusion. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed by 120 min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent to assess the degree of myocardial injury. Extent of myocardial infarct size and coronary flow rate was also measured. Remote renal preconditioning and erythropoietin preconditioning (5,000 IUkg−1, i.p.) attenuated ischemia-reperfusion-induced myocardial injury and produced cardioprotective effects. However, administration of diethyldithiocarbamic acid (150 mg kg−1i.p.), a selective NFkB inhibitor, and glibenclamide (5 mg kg−1i.p.), a selective KATP channel blocker, attenuated cardioprotective effects of remote preconditioning and erythropoietin preconditioning. However, administration of minoxidil (1 mg kg−1i.v.), a selective KATP channel opener, restored the attenuated cardioprotective effects of remote preconditioning and erythropoietin preconditioning in diethyldithiocarbamic acid pretreated rats. These results suggest that KATP channel is a downstream mediator of NFkB activation in remote preconditioning and erythropoietin preconditioning. Therefore, it may be concluded that erythropoietin preconditioning and remote renal preconditioning trigger similar signaling mechanisms for cardioprotection, i.e., NFkB activation followed by opening of KATP channels.