Angiotensin II type 1 receptor antagonist, TCV-116, prevents neointima formation in injured arteries in the dog

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 formati on in dog artery injured by a balloon catheter. Dogs were orally treated wi th 10 mg/kg TCV-116 or placebo twice a day for 5 weeks. After treatment wit h 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 grou p treated with placebo, neointima formation in the injured arteries was obs erved. The activities of angiotensin converting enzyme (ACE) and chymase in the injured carotid arteries were increased 2.56- and 3.26-fold compared w ith 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 mm(2), respectively, and this difference was significant. In conclusion, a n 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 .