title: Nonselective ETA/ETB receptor antagonist blocks proliferation of rat vascular smooth muscle cells after balloon angioplasty.
abstract: To elucidate the role of endothelin receptor subtypes in the abnormal proliferation of vascular smooth muscle cells (VSMC) associated with vascular injury, we have investigated the effects of a novel and potent nonselective ETA/ETB receptor antagonist (TAK-044) on the proliferation of rat VSMC in vitro and in vivo. TAK-044 dose-dependently inhibited DNA synthesis stimulated by 10(-7) M ET-1 in cultured rat VSMC from the late passage with the approximate IC50 of 6 x 10(-8) M. After balloon angioplasty, the neointimal lesion in the injured carotid arteries in the TAK-044-treated group (0.052 +/- 0.014 mm2) was significantly (p < 0.05) decreased compared to that in control group (0.26 +/- 0.045 mm2), while the medial surface area was not affected. The intima/media ratio in the TAK-044 group (31 +/- 6%) also significantly (p < 0.05) decreased from that of the control group (148 +/- 25%). Our data suggest that nonselective ETA/ETB receptor antagonists may be therapeutic potential for prevention against the intimal thickening associated with vascular injury.
authors.affiliation: Second Department of Internal Medicine, Tokyo Medical & Dental University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsujino
authors.forename: Y
authors.initials: Y
authors.lastname: Hirata
authors.forename: S
authors.initials: S
authors.lastname: Eguchi
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: F
authors.initials: F
authors.lastname: Chatani
authors.forename: F
authors.initials: F
authors.lastname: Marumo
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; C088196:TAK 044; C072247:cyclo(Trp-Asp-Pro-Val-Leu)