Application of Serial In Vivo Magnetic Resonance Imaging to Evaluate the Efficacy of Endothelin Receptor Antagonist SB 217242 in the Rat Carotid Artery Model of Neointima Formation

Background—Alleviating vascular restenosis after percutaneous transluminal angioplasty remains a formidable challenge. Although multiple factors have been implicated in the pathophysiology of this vascular remodeling disorder, only limited therapeutic success has been achieved. Endothelin (ET)-1 has recently been implicated in the pathogenesis of neointimal growth. We report the in vivo efficacy of SB 217242, a nonpeptide dual ETA/ETB receptor antagonist with high oral bioavailability, in the rat carotid artery balloon angioplasty model. Methods and Results—The lumen volumes of carotid arteries were estimated serially with magnetic resonance imaging (MRI) at baseline and at day 7 and day 14 after balloon catheter–induced denudation of the carotid arterial wall in the rat. Histomorphometric analysis was performed at day 14 after surgery to quantitate intimal hyperplasia. Statistical analysis was performed with ANOVA followed by post hoc Newman-Keuls multiple comparison test. In comparison to vehicle-treate...