Inducible and endothelial nitric oxide synthase distribution and expression with hind limb per-conditioning of the rat kidney.

INTRODUCTION

We recently reported that a series of brief hind limb ischemia and reperfusion (IR) at the beginning of renal ischemia (remote per-conditioning - RPEC) significantly attenuated the ischemia/reperfusion-induced acute kidney injury. In the present study, we investigated whether the nitric oxide synthase (NOS) pathway is involved in the RPEC protection of the rat ischemic kidneys.

MATERIAL AND METHODS

Male rats were subjected to right nephrectomy and randomized as: (1) sham, no additional intervention; (2) IR, 45 min of renal ischemia followed by 24 h reperfusion; (3) RPEC, four 5 min cycles of lower limb IR administered at the beginning of renal ischemia; (4) RPEC+L-NAME (a non-specific NOS inhibitor, 10 mg/kg, .) (5) RPEC + 1400W (a specific iNOS inhibitor, 1 mg/kg, .). After 24 h, blood, urine and tissue samples were collected.

RESULTS

The protective effect of RPEC on renal function, oxidative stress indices, pro-inflammatory marker expression and histopathological changes of kidneys subjected to 45 min ischemia were completely inhibited by pretreatment with L-NAME or 1400W. It was accompanied by increased iNOS and eNOS expression in the RPEC group compared with the IR group.

CONCLUSIONS

These findings suggest that the protective effects of RPEC on renal IR injury are closely dependent on the nitric oxide production after the reperfusion and both eNOS and iNOS are involved in this protection.