Protective effect of angiotensin II receptor blockage on rats with experimental diabetes nephropathy in early stage

OBJECTIVE: To investigate the possible mechanism of angiotensin II receptor blockage (Losartan) for the decreasing of proteinuria and the protection of renal function in diabetic rats. METHODS: Sixty Wistar rats were divided into 3 groups: Losartan treatment group, diabetes mellitus (DM) model group, and control group. All were treated accordingly for 4 weeks. 24 hours urine protein count, creatinin clearance rate (Ccr), mean arterial pressure (MAP), kidney weight/body weight, ET-1 in blood and urine, IV collagen and fibronectin (FN) in kidney tissue were determined at 1, 2, 4 weeks. RESULTS: In DM model group, the 24 hours urine protein count and MAP, compared with control, increased significantly (P < 0.05) and reached peak at 2 weeks; the decrease of Ccr and the increase of kidney weight/body weight were observed; meanwhile, by immunohistochemistry, increased expression levels of FN, IV collagen were shown in kidney tissues, especially on basement membrane, and significant increase of ET-1 level in blood and urine was also noted. In Losartan treatment group, all of MPA, 24 hours urine protein count, kidney weight/body weight and Ccr decreased, compared with those of model group; ET-1 in blood and urine decreased too, especially the decreasing of ET-1 in urine (P < 0.01). And the expression level of FN and IV collagen was just as small as that in control group. CONCLUSION: Losartan may play a role in inhibiting the synthesis and secretion of ET-1 in kidney and thus it will contribute to the decreasing of proteinuria and the protection of renal function.