1.Endothelin ETB receptor is involved in sex differences in the development of balloon injury-induced neointimal formation.
Kitada K1, Yui N, Koyama M, Kimura K, Suzuki R, Tanaka R, Mori T, Ohkita M, Matsumura Y. J Pharmacol Exp Ther. 2011 Feb;336(2):533-9. doi: 10.1124/jpet.109.165308. Epub 2010 Nov 12.
The purpose of this study was to evaluate the involvement of endothelin (ET)(B) receptor-mediated action in the sex differences in balloon injury-induced neointimal formation using the spotting-lethal rat, which carries a naturally occurring deletion in its ET(B) receptor gene. Male and female ET(B)-deficient and wild-type rats underwent balloon injury of the carotid artery. In the wild-type rats, the neointima/media ratio was significantly lower in females than in males, but this sex difference was attenuated by ovariectomy and restored by treatment with 17β-estradiol (20 μg/kg/day). In the ET(B)-deficient rats, the neointima/media ratio of the male and female rats was markedly increased to the same level, and this increase was not affected by ovariectomy or 17β-estradiol treatment. Treatment with (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine-6-carboxylic acid (J-104132) (10 mg/kg/day), an ET(A)/ET(B) dual receptor antagonist, markedly decreased the neointima/media ratio of the male wild-type rats and the male and female ET(B)-deficient rats, but not the female wild-type rats.
2.Inhibition of endothelin ETB receptor system aggravates neointimal hyperplasia after balloon injury of rat carotid artery.
Kitada K1, Yui N, Matsumoto C, Mori T, Ohkita M, Matsumura Y. J Pharmacol Exp Ther. 2009 Dec;331(3):998-1004. doi: 10.1124/jpet.109.157065. Epub 2009 Sep 8.
Endothelin-1 (ET)/ET(A) receptor system has been known to play an important role in the pathogenesis of neointimal hyperplasia after endothelial injury. However, the pathological role of endothelin ET(B) receptors on neointimal hyperplasia remains to be elucidated. In the present study, we investigated the pathological role of ET(B) receptors on neointimal hyperplasia in balloon-injured rat carotid arteries by pharmacological blockade with use of 2R-(4-propoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N-(2,6-diethylphenyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (A-192621), a selective ET(B) receptor antagonist, 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627), a selective ET(A) receptor antagonist, and (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine-6-carboxylic acid (J-104132), an ET(A)/ET(B) dual receptor antagonist.
