A Novel 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), Suppressed Intimal Hyperplasia after Balloon Injury

• Published in: The Journal of pharmacology and experimental therapeutics 2003-02, Vol.304 (2), p.841-844
• Main Authors: Takai, Shinji, Sakonjo, Hiroshi, Fukuda, Kohzo, Jin, Denan, Sakaguchi, Masato, Kamoshita, Keiichi, Ishida, Koichi, Sukenaga, Yoshikazu, Miyazaki, Mizuo
• Format: Article
• Language: English
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.102.042580

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 mm 2 , 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.