Valsartan inhibited HIF-1α pathway and attenuated renal interstitial fibrosis in streptozotocin-diabetic rats

Abstract: Aim: To investigate the effect of angiotensin II AT1 receptor blocker valsartan on hypoxia-inducible factor (HIF)-1α-mediated gene activation and its association with renal interstitial fibrosis (RIF) in diabetic nephropathy rats. Methods: Sprague-Dawley rats were randomly divided into 3 groups: control (C group), streptozocin-induced diabetic nephropathy (D group), and valsartan-treated D rats (T group). At end of the 4th, 8th and 12th week 6 rats from each group were sacrificed and blood, urine and kidneys were collected. Blood glucose, serum creatinine (Scr) and 24-h urinary protein were measured and kidneys were processed for Masson-stain as well as immunohistochemistry and real time-PCR analyses of the expressions of HIF-1α, and its target genes tissue inhibitor of metalloproteinase (TIMP)-1 and endothelin (ET)-1 in the kidney. Result: (1) At the 4th, 8th and 12th week, the areas of RIF were significantly increased in D and T groups, which was accompanied by higher levels of 24-h urinary protein, Scr, HIF-1α, ET-1 and TIMP-1 compared with C group. (2) At the 8th and 12th week, the above changes were significantly attenuated in T group compared with D group. Conclusions: Valsartan may reduce HIF-1α-mediated gene activation and consequently improve kidney damage in diabetic nephropathy rats. [Copyright &y& Elsevier]