Effect of Remote Ischemic Perconditioning on Renal Water and Salt Handling in Rats Subjected to Renal Ischemia/Reperfusion

Abstract

Renal ischemia/reperfusion (I/R) can lead to acute kidney injury, characterized by increased urine output and fractional excretion of sodium (FE(Na)). Previous studies have shown an improvement of these parameters when applying local ischemic preconditioning (IPC) to ischemic kidneys. Here we investigate the effect of remote ischemic perconditioning (rIPeC) on the renal water and salt handling in ischemic rat kidneys.Male Wistar rats were subjected to 37 min of unilateral renal ischemia and three days reperfusion. rIPeC was applied to the abdominal aorta. Blood and urine was collected on day 2 and 3 post‐operatively for clearance studies. The expression and localization of renal aquaporins (AQP1, AQP2, phosphorylated S256‐AQP2 and AQP3) and the sodium transports Na‐K‐ATPase and NKCC2 was analyzed using immunoblotting and immunohistochemistry (IHC). Finally, the renal injury was evaluated by morphological examination and detection of renal injury markers.As previously shown, renal I/R resulted in an increase in urine output and FE(Na) and a decrease in urine osmolality compared to Sham group. rIPeC attenuated all these parameters. The protein level of AQPs, Na‐K‐ATPase and NKCC2 was down regulated in the I/R group compared to Sham, and this reduction was attenuated in the I/R+rIPeC group. IHC showed weak labeling of AQP2 and pAQP2 in collecting ducts in I/R kidneys compared to sham kidneys. rIPeC increased the labeling and showed more apical localization of AQP2 and pAQP2.In conclusion, data suggests that rIPeC prevents dysregulation of renal water and salt handling by attenuating down regulation of aquaporins and sodium transporters in ischemic rat kidneys.