Abstract
(±)-1-(Cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116, Candesartan) and its active metabolite 2-ethoxy-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV-11974) are specific nonpeptide angiotensin AT 1 receptor antagonists. In the present study, the inhibitory potency of these two antagonists on the angiotensin II-induced responses in aortic vascular smooth muscle cells from Wystar Kyoto rats was investigated. The specific binding of 125I-angiotensin II to cells was inhibited by CV-11974 and TCV-116 with a half-maximal inhibitory concentration (IC 50) of 3 × 10 −11 M and 1 × 10 −9 M, respectively. CV-11974 and TCV-116 inhibited the angiotensin II-induced increase in [ 3H]thymidine incorporation with an IC 50 of 3 × 10 −10 and 5 × 10 −9 M, respectively. Both CV-11974 and TCV-116 (10 −7 M) completely blocked the angiotensin II-induced increase in c- fos mRNA. The inhibitory potency of the metabolite CV-11974 was about 30–100-fold higher than that of the prodrug TCV-116.
Published Version
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