Background: Although recent studies indicate that renal ischemic preconditioning (IPC) protects the kidney from\r\nischemia-reperfusion (I/R) injury, the precise protective mechanism remains unclear. In the current study, we\r\ninvestigated whether early IPC could upregulate hypoxia inducible transcription factor-1a (HIF-1a) expression and\r\ncould reduce endoplasmic reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric\r\noxide (NO) production would abolish these protective effects.\r\nMethods: Kidneys of Wistar rats were subjected to 60 min of warm ischemia followed by 120 min of reperfusion\r\n(I/R group), or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to intravenously\r\ninjection of NG-nitro-L-arginine methylester (L-NAME, 5 mg/kg) 5 min before IPC (L-NAME+IPC group). The results\r\nof these experimental groups were compared to those of a sham-operated group. Sodium reabsorption rate,\r\ncreatinine clearance, plasma lactate dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde\r\n(MDA), HIF-1a and nitrite/nitrate were determined. In addition, Western blot analyses were performed to identify\r\nthe amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress parameters.\r\nResults: IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt\r\nphosphorylation, eNOS, nitrite/nitrate and HIF-1a levels as compared to I/R group. Moreover, our results showed\r\nthat IPC increased the relative amounts of glucose-regulated protein 78 (GRP78) and decreased those of RNA\r\nactivated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptorassociated\r\nfactor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished these beneficial\r\neffects of IPC against renal I/R insults.\r\nConclusion: These findings suggest that early IPC protects kidney against renal I/R injury via reducing oxidative\r\nand ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production\r\ncontributing thus to HIF-1a stabilization. The beneficial impact of IPC was abolished when NO production is\r\ninhibited before IPC application.
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