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Estradiol-induced attenuation of pulmonary hypertension is not associated with altered eNOS expression.

机译:雌二醇诱导的肺动脉高压的减轻与eNOS表达的改变无关。

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Female rats develop less severe pulmonary hypertension (PH) in response to chronic hypoxia compared with males, thus implicating a potential role for ovarian hormones in mediating this gender difference. Considering that estrogen upregulates endothelial nitric oxide (NO) synthase (eNOS) in systemic vascular tissue, we hypothesized that estrogen inhibits hypoxic PH by increasing eNOS expression and activity. To test this hypothesis, we examined responses to the endothelium-derived NO-dependent dilator ionomycin and the NO donors S-nitroso-N-acetylpenicillamine and spermine NONOate in U-46619-constricted, isolated, saline-perfused lungs from the following groups: 1) normoxic rats with intact ovaries, 2) chronic hypoxic (CH) rats with intact ovaries, 3) CH ovariectomized rats given 17 beta-estradiol (E(2)beta), and 4) CH ovariectomized rats given vehicle. Additional experiments assessed pulmonary eNOS levels in each group by Western blotting. Our findings indicate that E(2)beta attenuated chronic hypoxia-induced right ventricular hypertrophy, pulmonary arterial remodeling, and polycythemia. Furthermore, although CH augmented vasodilatory responsiveness to ionomycin and increased pulmonary eNOS expression, these responses were not potentiated by E(2)beta. Finally, responses to S-nitroso-N-acetylpenicillamine and spermine NONOate were similarly attenuated in all CH groups compared with normoxic control groups. We conclude that the inhibitory influence of E(2)beta on chronic hypoxia-induced PH is not associated with increased eNOS expression or activity.
机译:与慢性雄性不育相比,雌性大鼠对慢性低氧的反应较不严重,因此暗示了卵巢激素在介导这种性别差异中的潜在作用。考虑到雌激素上调全身血管组织中的内皮型一氧化氮(NO)合酶(eNOS),我们假设雌激素通过增加eNOS的表达和活性来抑制低氧PH。为了检验该假设,我们检查了以下组中对U-46619限制的,分离的,灌注有盐水的肺对内皮源性NO依赖的扩张剂离子霉素和NO供体S-亚硝基-N-乙酰青霉胺和精胺NONOate的反应: 1)卵巢完整的常氧大鼠,2)卵巢完整的慢性低氧(CH)大鼠,3)给予17个雌二醇(E(2)beta)的CH卵巢切除大鼠和4)给予媒介物的CH卵巢切除大鼠。其他实验通过蛋白质印迹法评估了每组中的肺eNOS水平。我们的发现表明,E(2)β减弱了慢性低氧引起的右心室肥大,肺动脉重构和红细胞增多症。此外,尽管CH增强了对离子霉素的血管舒张反应性并增加了肺eNOS的表达,但这些反应并未被E(2)beta增强。最后,与正常氧对照组相比,所有CH组对S-亚硝基-N-乙酰青霉胺和精胺NONOate的反应均减弱。我们得出结论,E(2)β对慢性低氧诱导的PH的抑制作用与eNOS表达或活性增加无关。

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