@article {Kawamura1664, author = {M Kawamura and Z Terashita and H Okuda and Y Imura and A Shino and M Nakao and K Nishikawa}, title = {TCV-116, a novel angiotensin II receptor antagonist, prevents intimal thickening and impairment of vascular function after carotid injury in rats.}, volume = {266}, number = {3}, pages = {1664--1669}, year = {1993}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Inhibitory effects of TCV-116 [(+-)-1-(cyclohexyloxycarbonyloxy)ethyl2-ethoxy-1-[[2{\textquoteright}-(1H- tetrazol-5- yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate], a novel angiotensin II AT1 subtype receptor antagonist, on the proliferation of vascular smooth muscle cells and the impairment of endothelium-dependent vascular relaxation were examined in the rat carotid balloon injury model. DNA content in the carotid artery was increased 3 days after carotid balloon injury and reached a plateau 14 days after the injury. Beneficial effects of TCV-116 in this model were examined 14 days after the injury. Oral administration of TCV-116 at 1 and 10 mg/kg/day significantly inhibited the increase in DNA content by 69 and 85\%, respectively. Histological examination demonstrated that TCV-116 at 1 and 10 mg/kg significantly inhibited intimal thickening by 43 and 58\%, respectively. Cilazapril (10 mg/kg/day p.o.) also inhibited intimal thickening by 48\%. Contracting or relaxing vascular responses to phenylephrine or sodium nitroprusside did not differ between uninjured and injured arteries. However, acetylcholine-induced endothelium-dependent relaxation was greatly reduced in injured arteries; maximal relaxation was 6 +/- 2\% (n = 17). TCV-116 at 1 and 10 mg/kg significantly ameliorated the impairment of vascular relaxation; maximal relaxation was 25 +/- 8 (n = 7) and 51 +/- 12\% (n = 5), respectively. In uninjured arteries, L-NG-monomethyl arginine (300 microM), an inhibitor of endothelium-derived relaxing factor synthesis, inhibited acetylcholine (10 microM)-induced relaxation by 58 +/- 4\% (n = 5). Scanning electron micrographs demonstrated that TCV-116 (10 mg/kg/day) enhanced restoration of endothelial cells in the carotid artery 14 days after injury.(ABSTRACT TRUNCATED AT 250 WORDS)}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/266/3/1664}, eprint = {https://jpet.aspetjournals.org/content/266/3/1664.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }