Endothelin-1 promotes neointima formation after balloon angioplasty in the rat.
The long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA) is severely limited by the high incidence of vascular restenosis. Endothelin-1 (ET-1) has been implicated in the pathogenesis of this response, since circulating levels of this potent smooth-muscle mitogen are elevated after PTCA. Therefore, this study examined the effect of exogenous ET-1 administration on the development of stenotic lesions in the rat common carotid artery angioplasty model. Immediately after left common carotid artery balloon angioplasty, rats received a 30-min i.a. infusion of either saline vehicle (0.9% NaCl w/v) or ET-1 (17 pmol kg-1 min-1) via the left external carotid artery. Left and right common carotid arteries were removed 7 days later for quantitative image analysis. Balloon angioplasty caused significant neointima proliferation in left common carotid arteries, the extent of which was increased significantly by acute ET-1 treatment (approximately 65% greater neointima formation relative to saline-treated rats). ET-1 treatment had no effect on the geometry of contralateral right common carotid arteries. Therefore, these data support a role for ET-1 in the pathogenesis of vascular restenosis.
Douglas
S A
SA
Department of Cardiovascular Pharmacology (UW 2510), SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Ohlstein
E H
EH
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D017536:Carotid Artery, Common / Q000473:pathology; D016232:Endothelins / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000254:growth & development / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins