We have previously reported that organ cultured coronary arteries from market-age pigs (6-9 months of age) exhibit an enhanced contraction to the atherosclerotic-associated peptide, endothelin-1 (ET-1). The objective of this study was to investigate the interaction of 17beta-estradiol with ET-1 in organ cultured coronary arteries from older female pigs (3-4 years old). A cumulative concentration-response relationship (1 x 10(-9) M to 3 x 10(-7) M) was generated to ET-1, and the isometric tension measured in fresh and organ cultured (4 days at 37 degrees C) arterial rings that were each pre-incubated for 50 min in different concentrations (1 x 10(-9) M to 1 x 10(-5) M) of 17beta-estradiol. Compared to freshly used arteries, culturing induced a 2-fold increase in tension development to ET-1 (3 x 10(-7) M). Although 17beta-estradiol previously relaxed pre-constricted (with a 60 mM KCl solution) arteries, it did not affect the constrictive response to ET-1. Also, using an ET-1 ELISA we found that 17beta-estradiol did not effect ET-1 production in intact arteries. Our results indicate that 17beta-estradiol does not attenuate the production and constrictive properties of ET-1 in coronary arteries demonstrating a dedifferentiated cell phenotype.

译文

:我们以前曾报道过,来自适龄猪(6-9个月大)的器官培养的冠状动脉对动脉粥样硬化相关肽内皮素-1(ET-1)的收缩增强。这项研究的目的是调查17β-雌二醇与ET-1在成年雌性猪(3-4岁)的器官培养的冠状动脉中的相互作用。对ET-1产生了累积的浓度-响应关系(1 x 10(-9)M到3 x 10(-7)M),并在新鲜和器官培养中(在37摄氏度下4天)测量了等轴测张力。分别以不同浓度(1 x 10(-9)M到1 x 10(-5)M)的17beta-雌二醇预孵育50分钟的动脉环。与新鲜使用的动脉相比,培养引起向ET-1的张力发展增加了2倍(3 x 10(-7)M)。尽管17β-雌二醇以前可以放松预收缩(用60 mM KCl溶液)的动脉,但它并不影响对ET-1的收缩反应。此外,使用ET-1 ELISA,我们发现17β-雌二醇不会影响完整动脉中ET-1的产生。我们的研究结果表明17β-雌二醇不会减弱冠状动脉中ET-1的产生和收缩特性,表明去分化的细胞表型。

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