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

[1] CHAMLEY JH, 1979, PHYSIOL REV, V39, P1
[2] ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE
CHIRGWIN, JM
PRZYBYLA, AE
MACDONALD, RJ
RUTTER, WJ
[J]. BIOCHEMISTRY, 1979, 18 (24) : 5294 - 5299
[3] CHIU AT, 1990, J PHARMACOL EXP THER, V252, P711
[4] BIOCHEMICAL-CHARACTERIZATION OF 2 ANGIOTENSIN-II RECEPTOR SUBTYPES IN THE RAT
DEGASPARO, M
WHITEBREAD, S
MELE, M
MOTANI, AS
WHITCOMBE, PJ
RAMJOUE, HP
KAMBER, B
[J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1990, 16 : S31 - S35
[5] LOSARTAN INHIBITS THE ANGIOTENSIN II-INDUCED STIMULATION OF THE PHOSPHOINOSITIDE SIGNALING SYSTEM IN VASCULAR SMOOTH-MUSCLE CELLS
KO, Y
GORG, A
APPENHEIMER, M
WIECZOREK, AJ
DUSING, R
VETTER, H
SACHINIDIS, A
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1992, 227 (02): : 215 - 219
[6] EFFECTS OF AN ANGIOTENSIN-II RECEPTOR ANTAGONIST, CV-11974, ON ANGIOTENSIN-II-INDUCED INCREASES IN CYTOSOLIC-FREE CALCIUM-CONCENTRATION, HYPERPLASIA, AND HYPERTROPHY OF CULTURED VASCULAR SMOOTH-MUSCLE CELLS
KOH, E
MORIMOTO, S
TOMITA, J
RAKUGI, H
JIANG, BB
INOUE, T
NABATA, T
FUKUO, K
OGIHARA, T
[J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1994, 23 (02) : 175 - 179
[7] NODA M, 1993, BIOCHEM PHARMACOL, V46, P311
[8] SMOOTH MUSCLE CELL .2. GROWTH OF SMOOTH MUSCLE IN CULTURE AND FORMATION OF ELASTIC FIBERS
ROSS, R
[J]. JOURNAL OF CELL BIOLOGY, 1971, 50 (01) : 172 - +
[9] EXP3174, A METABOLITE OF LOSARTAN (MK-954, DUP-753) IS MORE POTENT THAN LOSARTAN IN BLOCKING THE ANGIOTENSIN-II-INDUCED RESPONSES IN VASCULAR SMOOTH-MUSCLE CELLS
SACHINIDIS, A
KO, Y
WEISSER, P
BRICKWEDDE, MKMZ
DUSING, R
CHRISTIAN, R
WIECZOREK, AJ
VETTER, H
[J]. JOURNAL OF HYPERTENSION, 1993, 11 (02) : 155 - 162
[10] SCHELLING P, 1991, J HYPERTENS, V9, P3

← 1 2 →