EFFECTS OF TCV-116 AND CV-11974 ON ANGIOTENSIN-II-INDUCED RESPONSES IN VASCULAR SMOOTH-MUSCLE CELLS

被引：12

作者：

FLESCH, M ^{[1
]}

KO, Y ^{[1
]}

SEUL, C ^{[1
]}

DUSING, R ^{[1
]}

FELTKAMP, H ^{[1
]}

VETTER, H ^{[1
]}

SACHINIDIS, A ^{[1
]}

机构：

[1] UNIV BONN, MED POLIKLIN, D-53111 BONN, GERMANY

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1995年 / 289卷 / 02期

关键词：

CV-11974; TCV-116; SMOOTH MUSCLE CELL; VASCULAR; CELL GROWTH; C-FOS;

D O I：

10.1016/0922-4106(95)90121-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

(+/-)-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 I-125-angiotensin II to cells was inhibited by CV-11974 and TCV-116 with a half-maximal inhibitory concentration (IC50) of 3 x 10(-11) M and 1 x 10(-9) M, respectively. CV-11974 and TCV-116 inhibited the angiotensin II-induced increase in [H-3]thymidine incorporation with an IC50 of 3 x 10(-10) and 5 x 10(-9) M, respectively. Both CV-11974 and TCV-116 (10(-7) M) completely blocked the angiotensin II-induced increase in c-fas mRNA. The inhibitory potency of the metabolite CV-11974 was about 30-100-fold higher than that of the prodrug TCV-116.

引用

页码：399 / 402

页数：4

共 15 条

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