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

Circulation
S ChandraE H Ohlstein

Abstract

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 ET(A)/ET(B) receptor antagonist with high oral bioavailability, in the rat carotid artery balloon angioplasty model. 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-treated animals, a 20% protection (P<0.05) from reduction was shown in the estimated lumen volume with long-term administration of SB 217242 (15 mg/kg BID p.o.). Histologic analyses indicated a 42% decrease (P<0.05) in neointimal growth. The MRI lumen volumes ...Continue Reading

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Citations

Dec 4, 2002·Nature Reviews. Drug Discovery·Giuseppe RemuzziAriela Benigni
Apr 25, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Michel Félétou, Paul M Vanhoutte
Aug 9, 2005·Journal of Proteome Research·Sudeep ChandraSteven Carr

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