Effects of candesartan early or late treatment on angiotensinⅡtype 1 and type 2 receptor expression in type 2 diabetic KK/Ta mice kidney

Abstract

Abstract: AIM: To investigate the effects of candesartan, an angiotensin II type 1 receptor blocker (ARB) on angiotensin II type 1 (AT1) and type 2 (AT2) receptor expression in type 2 diabetic KK/Ta mouse kidneys. METHODS: KK/Ta mice divided into three groups were treated with candesartan (4 mg·kg^-1·d^-1) or vehicle from 6 or 12 to 28 weeks of age. BALB/c mice(n=6) treated with vehicle were used as controls. Body weight, blood pressure, blood glucose,urinary microalbumin,urinary creatinine and serum creatinine were measured every four weeks.At 28 weeks, morphometric analysis including the whole glomerular area (WGA), glomerular tuft area (GTA), extracellular matrix area (ECMA) and intraglomerular cell nuclei number (NIGCN) was conducted, and renal expressions of AT1 and AT2 were evaluated by immunohistochemistry and immunofluorescence. RESULTS: KK/Ta mice developed higher body weight, blood glucose, and urinary microalbumin/creatinine ratio in KK/Ta mice at 28 weeks of age were significantly higher than that of BALB/c mice (427.49±89.37 mg/g vs. 9.54±3.25 mg/g,P<0.01). AT1 expression was upregulated, and AT2 expression was downregulated in KK/Ta kidneys with increased WGA, GTA, ECMA and NIGCN. Candesartan treatment has markedly reduced urinary microalbumin/ creatinine ratio (Early treatment group: 32.18±9.41 mg/g,Late treatment group: 53.20±7.26 mg/g,P<0.01). Treatment with candesartan inhibited AT1 expression and increased AT2 expression. Candesartan treatment reduced WGA, GTA, ECMA, NIGCN, and mean blood pressure. There were no significant differences between the two treatment groups (from 6 or 12 weeks). CONCLUSION: The results suggest that candesartan, an ARB, attenuated glomerular hypertrophy and mesangial matrix accumulation and subsequent albuminuria by down-regulating AT1 expression and up-regulating AT2 expression in type 2 diabetic KK/Ta mouse kidneys.

Key words: Diabetic nephropathy, Candesartan, KK/Ta mice, Angiotensin Ⅱ type 1 receptor, Angiotensin Ⅱ type 2 receptor

CLC Number:

R965.2

FAN Qiu-ling, ZHAO Xiao-ming, PU Shi, LI Sa-li, YANG Gang, JIANG Yi, WANG Li-ning. Effects of candesartan early or late treatment on angiotensinⅡtype 1 and type 2 receptor expression in type 2 diabetic KK/Ta mice kidney[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(6): 627-633.

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