Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/67689
標題: A reduction of unilateral ureteral obstruction-induced renal fibrosis by a therapy combining valsartan with aliskiren
作者: Wu, W.P.
Chang, C.H.
Chiu, Y.T.
Ku, C.L.
Wen, M.C.
Shu, K.H.
Wu, M.J.
關鍵字: direct renin inhibitor;angiotensin II receptor blocker;direct renin inhibition;ii receptor blocker;converting;enzyme-inhibition;randomized controlled-trial;angiotensin-ii;diabetic-nephropathy;interstitial fibrosis;ace-inhibition;dual;blockade;hypertension
Project: American Journal of Physiology-Renal Physiology
期刊/報告no:: American Journal of Physiology-Renal Physiology, Volume 299, Issue 5, Page(s) F929-F941.
摘要: 
Wu WP, Chang CH, Chiu YT, Ku CL, Wen MC, Shu KH, Wu MJ. A reduction of unilateral ureteral obstruction-induced renal fibrosis by a therapy combining valsartan with aliskiren. Am J Physiol Renal Physiol 299: F929-F941, 2010. First published August 4, 2010; doi:10.1152/ajprenal.00192.2010.-The protective effect of combination therapy with valsartan and aliskiren against renal fibrosis remains to be defined. This study was undertaken to examine the protective effects of the combination of valsartan and aliskiren against renal fibrosis induced by unilateral ureteral obstruction (UUO). Combination therapy with valsartan (15 mg . kg(-1) . day(-1)) and aliskiren (10 mg . kg(-1) . day(-1)), valsartan monotherapy (30 mg . kg(-1) . day(-1)), and aliskiren monotherapy (20 mg . kg(-1) . day(-1)) all significantly ameliorated the increase in blood urea nitrogen and the degree of hydronephrosis determined by the increase in weight and length of the obstructed kidney. The dose titration study and blood pressure measurement confirmed that the combination therapy provided a greater benefit independent of the vasodilatory effect. There were no significant changes in serum levels of creatinine, sodium, and potassium in UUO rats and any treatment groups. Combination therapy also attenuated UUO-related increases in the scores of tubular dilatation, interstitial volume, interstitial collagen deposition, alpha-smooth muscle actin, the activation of ERK 1/2, the infiltration of monocytes/macrophages, the mRNA expression of snail-1, and transforming growth factor-beta 1 to a greater extent compared with aliskiren or valsartan used alone. The mRNA expression of renin and the (pro) renin receptor significantly increased after UUO. Combination therapy and monotherapy of valsartan and aliskiren had a comparable enhancing effect on the mRNA expression of renin, whereas all these treatments did not affect the expression of the (pro) renin receptor. In conclusion, a direct renin inhibitor in conjunction with an angiotensin II receptor blocker exerts increased renal protection against renal fibrosis and inflammation during obstruction over either agent alone.
URI: http://hdl.handle.net/11455/67689
ISSN: 1931-857X
DOI: 10.1152/ajprenal.00192.2010
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