[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.


CONCLUSIONS
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.
Yang
Lichuan
L
Department of Nephrology, West China Hospital, Sichuan Univerdity, Chengdu 610041, China.
Fan
Junming
J
Mi
Xuhua
X
Liu
Xianrong
X
Xu
Guozhang
G
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D019332:Endothelin-1 / Q000097:blood / Q000652:urine; D007677:Kidney Function Tests; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D057911:Angiotensin Receptor Antagonists; D019332:Endothelin-1; D019808:Losartan