Idoxifene causes endothelium-dependent, nitric oxide-mediated vasorelaxation in male rats.
Idoxifene causes endothelium-dependent, nitric oxide-mediated vasorelaxation in male rats.
复制标题
Idoxifene 在雄性大鼠中引起内皮依赖性、一氧化氮介导的血管舒张。
DOI：
10.1016/s0014-2999(02)01821-6
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发表时间：
2002
影响因子：
5
通讯作者：
Yue,Tian-Li
中科院分区：
文献类型：
--
作者：
Christopher,TheodoreA;Lopez,BernardL;Stillwagon,JasonC;Gao,Feng;Gao,Erher;Ma,Xin-Liang;Ohlstein,EliotH;Yue,Tian-Li
Selective estrogen receptor modulators are estrogen-like compounds that lack the deleterious effects of estrogen. The present study was designed to determine whether idoxifene, a new selective estrogen receptor modulator, may have a vasodilatory effect on aortic vessels from male animals, and if so, to investigate the mechanism (i.e., endothelium-independent, direct vasorelaxation vs. endothelium-dependent, nitric oxide mediated vasorelaxation) by which idoxifene may exert its vasodilatory effect. Superior mesenteric arterial rings from adult male Sprague–Dawley rats were suspended in Krebs–Henseleit ring baths. Rings were contracted with 50 nM U-46619 (9,11-epoxymethano-PGH2), a thromboxane A2mimetic. Cumulative dose–response vasorelaxation to idoxifene (0.01 to 3 μM) was studied in the presence and absence of 200 μM Nω-nitro-l-arginine methyl ester (l-NAME, a nitric oxide synthase (NOS) inhibitor). The results obtained from idoxifene were compared with those from 17β-estradiol. Our experimental results demonstrated that addition of idoxifene to superior mesenteric arterial rings isolated from male rats resulted in a dose-dependent vasorelaxation in the range of 0.1 μM (minimal vasodilatory concentration) to 3 μM (maximal vasodilatory concentration). Pre-treatment with l-NAME to block nitric oxide (NO) production virtually abolished idoxifene-induced vasodilatation, indicating that idoxifene caused an NO-mediated vasorelaxation in vessels from male animals. Addition of 17β-estradiol also resulted in an endothelium-dependent vasorelaxation in aortic rings from male rats. However, these vessels were 30-fold less sensitive to 17β-estradiol than to idoxifene in their vasorelaxation responses. Taken together, these results demonstrate that selective estrogen receptor modulators are superior to traditional estrogen in their vascular protection and may thus have potential therapeutic use in protection against cardiovascular disease, especially in male patients.
