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The effects of erythropoietin (EPO) alone or in conjunction with ischemic preconditioning (IPC) on nitric oxide synthase as well as comparing their effects on oxidative stress and proinflammatory cytokines are studied. Rats underwent bilateral renal ischemia of 50 min followed by 24 h reperfusion. They were administered EPO (5000 iu/kg i.p.) and/or subjected to IPC and sacrificed after 24 h, then plasma and tissue samples were obtained. Treatment of either EPO or IPC and their combination attenuates oxidative stress, decreases histological damages, inhibits proinflammatory response, and up-regulates iNOS and eNOS gene expression compared to IR group. In addition, EPO+IPC and EPO treatment produced significant up-regulation in iNOS gene expression compared to IPC group. In IPC and EPO+IPC groups, more powerful effect on up-regulation of eNOS gene expression was shown compared to EPO group. Our findings suggest that treatment with EPO or IPC and their combination improve renal function and preserve tubular damage induced by IR injury. These advantageous effects were closely related to reducing oxidative stress, suppressing proinflammatory response and enhancing generation of NO. IPC was more powerful in enhancement of eNOS gene expression compared to EPO that was more effective in increasing of iNOS gene expression.

general physiology and biophysics

Up-regulation of nitric oxide synthases by erythropoietin alone or in conjunction with ischemic preconditioning in ischemia reperfusion injury of rat kidneys