Effects of valsartan and benazepril on glomerulosclerosis in rats with 5/6 nephrectomy

Abstract

Abstract: AIM: To observe and compare the improvement of glomerul-osclerosis in rats with 5/6 nephrectomy by valsartan and benazepril.METHODS: Thirty Sprague-Dawley male rats were selected and performed five-sixths nephrectomy to produce chronic renal failure model.Two weeks after the surgery, the rats were randomly divided into model group, valsartan group and benazepril group, and established a shame group serving as normal control.The weight, blood pressure, blood uria nitrogen (BUN) and serum creatinine were measured on the sixth week after operation, then the rats were killed to take the kidneys for pathological histological observation. Immunohistochemistry was used to examine the expression of TGF-β₁ protein and fibronectin (FN) and collagen IV in glomeruli.RESULTS: As compared with model group, systolic pressure decreased (P<0.01) and renal function was ameliorated in two treatment groups, as well as the extent of glomerular mesangial proliferation, glomerulosclerosis index (GSI) decreased significantly (P<0.01).Immunohistochemistry staining indicated that there was an decreasing expression of TGF-β₁, FN and collagen IV in glomeruli in two treatment groups compared with model group (P<0.01).CONLUSION: The renoprotective effect of valsartan on chronic experiment renal failure rats is similar as benazepril.valsartan and benazepril can improve glomerulosclerosis by decreasing the expression of TGF-β₁, FN and collagen IV in glomeruli.

Key words: angiotensin converting enzyme, angiotensin receptor antagonist, glomerlosclerosis, transforming growth factorβ₁, extracellular matrix

CLC Number:

R965.1

YANG Li-Cai, ZHANG Dao-You, ZHANG Hui, ZHU Gui-Lan, GAO Chao-Qing. Effects of valsartan and benazepril on glomerulosclerosis in rats with 5/6 nephrectomy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(8): 914-918.

References

1 Noda M, Fukuda R, Matsuo T, Ohta M, Nagano H, Imura Y, et al.Effects of Candesartan cilexetil (TCV-116) and enalapril in 5 6 nephrectomized rats[J].Kidney Int, 1997;52(suppl63):136-9
2 Lacourciere Y, Belarger A, Godin C, Halle JP, Ross S, Wright N, et al.Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy[J].Kidney Int, 2000;58(2):762-7
3 Andersen S, Tarnow L, Rossing P, Hansen BV, Parving HH. Renoprotective effects of angiotensin Ⅱ receptor blockade in type I diabetic patients with diabetic nephropathy[J].Kidney Int, 2000;57(2):601-6
4 Raij L, Azar S, Keane W.Mesangial immune injury, hypertension, and progressive glomerular damage in dah1 rats[J].Kidney Int, 1984;26(2):137-43
5 邹万忠.肾活检病理图鉴[M].北京:人民卫生出版社,2000:55
6 Isaka Y, Fujiwara Y, Ueda N, Kaneda Y, Kamada T, Imai E, et al.Glomeruloscerosis induced by in vivo transfection of transforming growth factor or platelet-derived growth factor gene into the rat kidney[J].J Clin Inest, 1993;92(6):2597-603
7 Wolny A, Clozel JP, Rein J, Mory P, Vogt P, Turino M, et al.Functional and biochemical analysis of angiotensinⅡ-forming pathways in the human heart[J].Circ Res, 1997;80(2):219-27
8 Schmitz D, Berk BC.Angiotensin Ⅱ signal transduction stimulation of mutiple mitogen activated protein kinase pathways[J]. Trends EndocrinolMetab, 1997;8(2):261-6
9 Kagami S, Border WA, Miller DE, Noble NA.Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells[J].J Clin Invest, 1994;93(6):2431-7
10 黄洁, 李一石, 孙兴昌.依贝沙坦与苯那普利治疗原发性高血压比较[J].中国临床药学志, 2001;10(2):205-7
11 Obata J, Nakamura T, Kuroyanagi R, Yoshida Y, Guo D, Inagami T, et al.Candesartan prevents the progression of glomerulosclerosis in genetic hypertensive rats[J].Kidney Int, 1997;52(suppl 63):229-31
12 Nakamura T, Obata J, Kimura H, Ohno S, Yoshida Y, Kawachi H.Blocking angiotensin Ⅱ ameliorates proteinuria and glomerular lesions in progressive mesangioproliferative glomerulonephritis[J].Kidney Int, 1999;55(3):877-89
13 Enz J, Oshrain C, Henry D, Avery C, Chiang YT, Gatlin M. Valsartan, a new angiotensin Ⅱ receptor antagonist :a doubleblind study comparing the incidence of cough with lisinopril and hydrochlorothiazide[J].J Clin Pharmacol, 1997;37(2):101-7

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