Abstract
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.
Footnotes
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Supported by Grant-in-Aid 12770048 for Encouragement of Young Scientists from the Japanese Ministry of Education, Science, Sports, and Culture.
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DOI: 10.1124/jpet.102.042580
- Abbreviations:
- ACE
- angiotensin-converting enzyme
- AT1 receptor
- angiotensin II type 1 receptor
- NK3201
- 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[{3,4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl]acetamide
- Received August 1, 2002.
- Accepted October 4, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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