Mizuo Miyazaki (1), Naotaka Shiota (1), Hiroshi Sakonjo (1,2) and Shinji
(1) Department of Pharmacology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan
(2) Environmental Biological Life Science Research Center (BILIS), Minakuchi-cho, Koka-gun, Shiga 528-0052, Japan
Abstract: We investigated the effect of an angiotensin (Ang) II antagonist, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)
biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116), on neointima formation in dog artery injured by a balloon catheter. Dogs were orally treated with 10 mg/kg TCV-116 or placebo twice a day for 5 weeks. After treatment with these drugs for 1 week, the right carotid artery was injured by a balloon catheter. The left carotid artery was regarded as the control. In the group treated with placebo, neointima formation in the injured arteries was observed. The activities of angiotensin converting enzyme (ACE) and chymase in the injured carotid arteries were increased 2.56- and 3.26-fold compared with those in the non-injured arteries, respectively. The neointimal area in dogs treated with placebo and TCV-116 were 0.51+/-0.07 and 0.21+/-0.07 mm2, respectively, and this difference was significant. In conclusion, an Ang II antagonist, TCV-116, prevented neointima formation by blocking the action of Ang II generated by both ACE and chymase in the injured arteries.
Keywords: Angiotensin II, Angiotensin converting enzyme, Chymase, AT1-receptor antagonist