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[Protective effect of angiotensin II receptor blockage on rats with experimental diabetes nephropathy in early stage]
Lichuan Yang1, Junming Fan, Xuhua Mi
1Department of Nephrology, West China Hospital, Sichuan Univerdity, Chengdu 610041, China.
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.
Insights
Losartan treatment reduced proteinuria and protected kidney function in diabetic rats by inhibiting endothelin-1 (ET-1) synthesis and secretion. This suggests a novel therapeutic mechanism for diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Context:
- Diabetic nephropathy is a major complication of diabetes mellitus.
- Proteinuria and declining renal function are key indicators of diabetic kidney disease.
- Endothelin-1 (ET-1) is implicated in the pathogenesis of diabetic nephropathy.
Purpose:
- To investigate the mechanism by which Losartan, an angiotensin II receptor blocker, reduces proteinuria and protects renal function in a rat model of diabetes mellitus.
- To assess the impact of Losartan on markers of kidney damage and ET-1 levels.
Summary:
- Diabetic rats exhibited increased proteinuria, mean arterial pressure (MAP), kidney weight, and elevated levels of ET-1, collagen IV, and fibronectin compared to controls.
- Losartan treatment significantly reduced proteinuria, MAP, kidney weight, and improved creatinine clearance (Ccr) in diabetic rats.
- Losartan administration led to decreased ET-1 levels in blood and urine, and normalized collagen IV and fibronectin expression in kidney tissue.
Impact:
- Losartan may exert renoprotective effects in diabetic nephropathy by inhibiting ET-1 synthesis and secretion.
- These findings highlight a potential therapeutic strategy for managing diabetic kidney disease.
- Further research can explore Losartan's efficacy in human diabetic nephropathy patients.
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