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.