A single treatment with a specific chymase inhibitor, TY-51184, prevents vascular proliferation in canine grafted veins.
In this study, we evaluated whether a specific chymase inhibitor, TY-51184 (2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl]oxazole-4-carboxylicacid), prevents the vascular proliferation in canine grafted veins. In the placebo-and chymase inhibitor-treated groups, the external jugular vein was infiltrated with saline and 10 microM TY-51184, respectively, and then it was grafted to the ipsilateral carotid artery. The non-surgical dogs were used as the control group. By 28 days after grafting, the chymase and ACE activities were significantly increased in the injured arteries. TY-51184 significantly reduced the chymase activity in the grafted veins, while it did not affect the ACE activity. The intimal areas in the placebo- and TY-51184-treated groups were 3.32 +/- 0.16 and 1.96 +/- 0.52 mm(2), respectively, and this difference was significant. The ratios of intimal area to medial area in the placebo- and TY-51184-treated groups were 66.8 +/- 3.5% and 34.9 +/- 9.2%, respectively, and this difference was also significant. There was a significant relationship between vascular proliferation and chymase activity, but not ACE activity. In this study, we demonstrated that a single treatment with a specific chymase inhibitor, TY-51184, could prevent the vascular proliferation in canine grafted veins.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Osaka, Japan. pha010@art.osaka-med.ac.jp
Jin
Denan
D
Sakaguchi
Masato
M
Miyazaki
Mizuo
M
D000818:Animals; D002339:Carotid Arteries / Q000601:surgery; D002455:Cell Division / Q000187:drug effects*; D053818:Chymases; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D007601:Jugular Veins / Q000187:drug effects / Q000473:pathology / Q000637:transplantation; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014680:Veins / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*
C487109:2-(4-(5-fluoro-3-methylbenzo(b)thiophen-2-yl)sulfonamide-3-methanesulfonylphenyl)oxazole-4-carboxylic acid; D010080:Oxazoles; D013449:Sulfonamides; D012697:Serine Endopeptidases; D053818:Chymases