AimTo discuss the role of endothelial dysfunction in the kidney damage induced by hyperuricemia.Methods36 male Wister rats were randomly divided into three groups, namely control group, hyperuricemia model group, benzbromarone treatment group(n=12).Application of Oteracil potassium(uricase inhibitor ) and high yeast feeding were used to establish the hyperuricemia model.In addition to the same treatment,the treatment group were added benzbromarone to control hypeuricemia.Control group were fed normal diet and tap water, at the weekend of 2,4,6, blood uric acid and creatinine level were tested.All rats were sacrificed at the end of 6 weeks, HE and Masson staining of renal organizations were applied to observe the pathological changes, and measure the interstitial fibrosis area.Endothelial nitric oxide synthase (eNOS), endothelin-1(ET-1) and hypoxia inducible factor-1α(HIF-1α) expressions in renal interstitial tubular were detected by immunohistochemistry.ResultsAfter 2 weeks the blood uric acid level in model group was higher than that of the control group and treatment group.At the end of 6 weeks, the serum creatinine level in the model group was much higher than that of the control group and the treatment group, there was no obvious difference between the two latter groups.The renal interstitial fibrosis was more serious than that of the normal control group and the treatment group.The nitric oxide synthase expression in the model group was significantly lower than that in the control group and treatment group, while both the endothelin-1 and hypoxia inducible factor-1α expression in the model group was significantly higher than that in the control group and treatment group.ConclusionHyperuricemia can reduce the sy-nthesis of nitric oxide synthase but increase the production of endothelin-1 in the renal interstitial vascular endothelial cells, thus affecting the endothelial function of renal interstitial vascular and leading to renal interstitial fibrosis through an mechanism of ischemia and hypoxia.