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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1994-5-12
pubmed:abstractText
Proliferation of smooth muscle cells within the intima plays a key role in vascular occlusive disorders such as atherosclerosis and restenosis following balloon angioplasty. Among the factors that may be important in the development of vascular lesions, several authors have reported that the local angiotensin system participates in modulating the proliferation of smooth muscle cells after arterial injury. This study was therefore designed to characterize the antagonistic properties and to investigate the antiproliferative effect of a newly developed non-peptide angiotensin II AT1 receptor antagonist, SR 47436. This compound is a potent and competitive antagonist of the binding of [125I]angiotensin II to its receptor on cultured human aortic smooth muscle cells, exhibiting an IC50 value of 1.7 +/- 0.6 nM. SR 47436 was 10-fold more potent than DuP 753 (Losartan) (IC50 = 20.8 +/- 3.7 nM). In these same cells, SR 47436 potently inhibited the angiotensin II-induced [Ca2+]i increase (IC50 = 0.53 +/- 0.13 vs. 7.4 +/- 1.3 nM for DuP 753). Angiotensin II is a potent mitogen for human aortic smooth muscle cells in culture, exhibiting a maximum proliferative response at 1 microM. SR 47436 and Losartan prevented angiotensin II-induced proliferation of these cells in a dose-dependent manner (IC50 = 0.32 +/- 0.09 and 0.71 +/- 0.08 microM, respectively). SR 47436 displayed a marked in vitro inhibition of serum-induced smooth muscle cell proliferation (IC50 = 5.5 +/- 0.8 microM). A selective AT2 receptor antagonist, PD 123177 did not affect angiotensin II-induced responses in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
251
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-50
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Effect of SR 47436, a novel angiotensin II AT1 receptor antagonist, on human vascular smooth muscle cells in vitro.
pubmed:affiliation
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
pubmed:publicationType
Journal Article