Document Detail


A novel chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[,4-dioxo-1-phenyl-7-(2-pyridyloxy)]2-heptyl]acetamide (NK3201), suppressed intimal hyperplasia after balloon injury.
MedLine Citation:
PMID:  12538841     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we investigated whether an orally active chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl]acetamide (NK3201), prevents intimal hyperplasia in carotid arteries injured by a balloon catheter in dog. Each dog was administered NK3201 (1 mg/kg per day, p.o.) or placebo beginning 5 days before balloon injury and continuing through the experiments. Four weeks after balloon injury, NK3201 did not affect the plasma renin and angiotensin-converting enzyme activities. The chymase activity was significantly increased in the injured arteries, whereas the angiotensin-converting enzyme activity was not. NK3201 significantly reduced the chymase activity in the injured arteries. The intimal area in the placebo- and NK3201-treated group and was 0.46 +/- 0.06 and 0.24 +/- 0.04 mm2, respectively, and this difference was significant. In this study, we demonstrated for the first time that a chymase inhibitor prevented the development of intimal hyperplasia in the balloon-injured arteries.
Authors:
Shinji Takai; Hiroshi Sakonjo; Kohzo Fukuda; Denan Jin; Masato Sakaguchi; Keiichi Kamoshita; Koichi Ishida; Yoshikazu Sukenaga; Mizuo Miyazaki
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  304     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-01-22     Completed Date:  2003-03-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  841-4     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan. pha010@art.osaka-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Acetamides / pharmacology*,  therapeutic use
Animals
Balloon Dilatation / adverse effects*
Carotid Artery, Common / drug effects*,  enzymology,  pathology*
Chymases
Dogs
Hyperplasia
Pyrimidines / pharmacology*,  therapeutic use
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / pharmacology*,  therapeutic use
Tunica Intima / drug effects*,  enzymology,  injuries,  pathology*
Chemical
Reg. No./Substance:
0/Acetamides; 0/NK3201; 0/Pyrimidines; 0/Serine Proteinase Inhibitors; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.39/Chymases

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


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