Vasoprotective effects of an endothelin receptor antagonist in ovariectomized female rats

LIFE SCIENCES

卷:118

Article

Kitada, Kento^1,2  Yui, Nozomi¹  Mori, Tatsuhiko³  Ohkita, Mamoru¹  Matsumura, Yasuo¹ 

[1] Osaka Univ Pharmaceut Sci, Lab Pathol & Mol Pharmacol, Osaka 580, Japan

[2] Kagawa Univ, Dept Pharmacol, Takamatsu, Kagawa 760, Japan

[3] Osaka Med Coll, Dept Internal Med 3, Osaka, Japan

关键词: Balloon injury;    Endothelin-1;    Angiotensin II;    Estrogen;    Neointimal formation;   

DOI  :  10.1016/j.lfs.2014.01.009

来源: Elsevier

【 摘 要 】

Aims: The effects of hormone replacement therapy with estrogen on cardiovascular disease in postmenopausal women are still controversial. In the present study, we examined the effects of an endothelin (ET) receptor antagonist (ERA) and/or angiotensin receptor blocker (ARB) on neointimal formation following vascular injury in ovariectomized (OVX) female rats. Main methods: Female rats were divided into intact female and OVX groups. The right carotid artery was subjected to balloon injury, and harvested 2 weeks later. Key findings: In the intact female groups, treatment with ARB (L-158809; 1 mg/kg/day) for two weeks after the injury significantly decreased neointimal formation, whereas treatment with the ERA (J-104132; 10 mg/kg/day) did not affect neointimal formation. On the other hand, the ERA markedly decreased neointimal formation after the injury in the OVX groups; however, neointimal formation was not significantly improved by the ARB treatment. In addition, the combined treatment with 17 beta-estradiol (20 mu g/kg/day) or the ERA and ARB markedly suppressed neointimal formation after the balloon injury in the OVX groups, whereas no combinational effects were observed due to the combined treatment with 17 beta-estradiol and the ERA. Significance: These results suggest that ERAs have estrogen-like vasoprotective effects on neointimal formation following balloon injury in OVX rats. ERAs may be useful as an alternative therapy to prevent vascular disease in postmenopausal women. (C) 2014 The Authors. Published by Elsevier Inc.

【 授权许可】

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