Protective effect of image-arginine on hypercholesterolemia-enhanced renal ischemic injury Original Research Article

The effects of hypercholesterolemia on ischemic renal failure were evaluated in rats subjected to 60 min of left renal artery clamping and contralateral nephrectomy. One group of rats (HC) was kept on a cholesterol-supplemented diet for 3 weeks before renal injury and compared to a group fed a regular diet (ND). Two days after renal ischemia, inulin clearance (Cin, ml/min per 100 g BW) was lower in HC-rats (0.033±0.011) than in ND-rats (0.227±0.037; P<0.01). indicating that hypercholesterolemia potentiated renal ischemic injury. Twenty-one days after renal ischemia the Cin of HC-rats did not differ from ND-rats, suggesting that hypercholesterolemia did not limit late recovery. Since nitric oxide production is impaired in HC, image-arginine (50 mg/kg BW i.v.) was administered immediately after ischemia. Two days after ischemia, image-arg did not protect ND-rats from ischemia, while the Cin and renal blood flow were higher in image-arg-treated HC rats than in untreated HC rats (Cin=0.125±0.013 rats vs. 0.033±0.011; P<0.001) (RBF=3.96±0.64 vs. 2.40±0.20 ml/min per 100 g BW; P<0.05), indicating that image-arg protects HC rats from renal ischemia. The administration of image-arginine to ND rats induced a significant decrease of the Cin and a significant increase of FE H2O, FE Na and FE K compared to the image-arginine and not treated groups. Cultures of inner medullary collecting duct cells from ND rats were resistant to 24-h hypoxia. In contrast, IMCD cell cultures from HC rats showed higher LDH release after 24-h hypoxia than normoxic cells (69.2±3.4 vs. 30.9±3.6%, P<0.001); 1 mM image-arg added to the medium attenuated LDH release (44.3±2.4%, P<0.01). These data demonstrate that HC predisposes renal tubular cells to hypoxic injury and image-arg protects cells of HC.