Document Detail


HR 720, a novel angiotensin receptor antagonist inhibits the angiotensin II-induced trophic effects, fibronectin release and fibronectin-EIIIA+ expression in rat aortic vascular smooth muscle cells in vitro.
MedLine Citation:
PMID:  8996227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to evaluate the direct trophic effects of angiotensin II (AII) on rat vascular smooth muscle cells obtained from a single cellular isolate. Cell volume, protein synthesis, fibronectin (FN) release and FN-EIIIA+ mRNA isoform expression were analyzed in parallel. The effects of HR 720, a novel AT1 angiotensin receptor antagonist with some AT2 receptor affinity, were compared with those of selective AT1 antagonist EXP 3174. Both HR 720 and EXP 3174 inhibited in a concentration-dependent manner the maximum increase in cell volume induced by 10(-9) M Sar1-All (IC50 = 0.49 x 10(-9) M and 0.79 x 10(-9) M, respectively). Maximum [3H]leucine incorporation was also achieved at 10(-9) M All. HR 720 blocked the increase in protein synthesis with potency similar to EXP 3174; the respective IC50 values were 1.04 x 10(-9) M and 1.36 x 10(-9) M. All dose-dependently increased FN release, which was also equally inhibited by about 50% with both compounds at 10(-6) M. Furthermore, All enhanced FN-EIIIA+ mRNA in rat vascular smooth muscle cells (VSMC), which indicated a modulation of FN isoform expression which was inhibited by angiotensin II antagonists. In conclusion, All induced parallel and concentration-dependent increases in cell volume, protein synthesis, FN release and FN-EIIIA+ mRNA expression in vascular smooth muscle cells. These effects appeared to be essentially mediated by AT1 receptor stimulation as indicated by the equal inhibitory effects of HR 720 and EXP 3174.
Authors:
F W Dunn; M H Roux; F Farhadian; K Sabri; C Ossart; J L Samuel; L Rappaport; G Hamon
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  280     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-02-10     Completed Date:  1997-02-10     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  447-53     Citation Subset:  IM    
Affiliation:
Centre de recherche Roussel-Uclaf, Romainville, France.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / antagonists & inhibitors*
Animals
Aorta, Thoracic / drug effects
Biphenyl Compounds / pharmacology*
Cells, Cultured
Fibronectins / genetics,  secretion*
Imidazoles / pharmacology*
Leucine / metabolism
Male
Muscle, Smooth, Vascular / cytology,  drug effects*
RNA, Messenger / analysis
Rats
Rats, Sprague-Dawley
Receptors, Angiotensin / antagonists & inhibitors*
Tetrazoles / pharmacology
Chemical
Reg. No./Substance:
0/Biphenyl Compounds; 0/Fibronectins; 0/Imidazoles; 0/RNA, Messenger; 0/Receptors, Angiotensin; 0/Tetrazoles; 0/fonsartan; 11128-99-7/Angiotensin II; 124750-92-1/EXP3174; 61-90-5/Leucine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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