Orally active endothelin receptor antagonist BMS-182874 suppresses neointimal development in balloon-injured rat carotid arteries

Journal of Cardiovascular Pharmacology
P FerrerS Moreland

Abstract

Vascular smooth muscle cell (SMC) proliferation is an important component in the development of restenosis. Because endothelin (ET) has been reported to act as an SMC mitogen, we postulated that the orally active ETA receptor antagonist BMS-182874 would suppress the development of the intimal lesion that develops in rat carotid arteries after balloon injury. Using cultured rat aortic SMC, we noted that ET-1-stimulated increases in [3H]thymidine incorporation were blocked by BMS-182874. To determine the effect of the drug on intimal lesion formation, we treated rats with BMS-182874 (100 mg/kg orally, p.o.) or vehicle once daily for 3 weeks, beginning 1 week before balloon injury. Two weeks after injury, drug-treated rats had a 35% decrease in lesion area and a 34% decrease in the lesion/media ratio as compared with the vehicle-treated rats. In situ hybridization (ISH) analysis of balloon-injured rat carotid arteries showed an increase in ETA receptor mRNA. These data support the concept that ETA receptor activation contributes to intimal lesion formation by promotion of SMC proliferation and suggest a potential use for ETA receptor antagonists in the amelioration of hyperproliferative vascular diseases, including restenosis.

Citations

Jan 24, 1998·Biochemical and Biophysical Research Communications·K A Peifley, J A Winkles
Dec 21, 2000·International Journal of Cardiology·Y TanakaY Mitsui
Nov 21, 2001·Current Opinion in Pharmacology·A P Davenport, J J Maguire
Mar 17, 1999·British Journal of Pharmacology·J J Maguire, A P Davenport
Apr 3, 2012·Cardiovascular Research·Nicholas S KirkbyPatrick W F Hadoke
Jan 5, 2002·Hypertension Research : Official Journal of the Japanese Society of Hypertension·S MinamiT Hashimoto
Jun 23, 2001·Drugs & Aging·M P Love, J J McMurray
Oct 24, 1998·Journal of Vascular Surgery·K E PorterN J London
Sep 10, 2009·The Journal of Pharmacology and Experimental Therapeutics·Kento KitadaYasuo Matsumura
May 22, 1998·Journal of Cardiovascular Pharmacology·P PicardD J Stewart
Oct 17, 2003·Coronary Artery Disease·Arshia Noori, Samer Kabbani
Dec 8, 2004·Diabetes/metabolism Research and Reviews·Gen FukudaSubrata Chakrabarti

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