Nascimento C A, Kauser K, Rubanyi G M
University of Sao Paulo, Sao Paulo, Brazil 01246-903.
Am J Physiol. 1999 May;276(5):H1788-94. doi: 10.1152/ajpheart.1999.276.5.H1788.
17beta-Estradiol prevents early vascular lesion development and may also affect advanced atherosclerosis. To test the antiatherosclerotic effect of estrogen under conditions that resemble more advanced human atherosclerosis with severe endothelial dysfunction, we have investigated the effect of 17beta-estradiol in hypercholesterolemic rabbits treated with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Chronic L-NAME administration attenuated endothelial nitric oxide (EDNO)-mediated vascular responses leading to significantly accelerated atherosclerotic plaque development. 17beta-Estradiol treatment alone inhibited aortic lesion formation with concurrent increase in EDNO-mediated responses. The beneficial effect of estrogen persisted in the L-NAME-treated rabbits, suggesting that the antiatherogenic action of 17beta-estradiol involves NO-independent mechanisms as well. Serum cholesterol levels were not altered by any of the treatments. 17beta-Estradiol treatment significantly increased EDNO production under these conditions as well. The reduction in plaque size by 17beta-estradiol was always accompanied by increased EDNO production, suggesting a strong association between these two events. The results demonstrate that estrogen treatment may exert protection against atherosclerosis even in patients with severe endothelial dysfunction.
17β-雌二醇可预防早期血管病变的发展，也可能影响晚期动脉粥样硬化。为了在更接近伴有严重内皮功能障碍的晚期人类动脉粥样硬化的条件下测试雌激素的抗动脉粥样硬化作用，我们研究了17β-雌二醇对用一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）治疗的高胆固醇血症兔的影响。长期给予L-NAME会减弱内皮源性一氧化氮（EDNO）介导的血管反应，导致动脉粥样硬化斑块发展显著加速。单独使用17β-雌二醇治疗可抑制主动脉病变形成，同时增加EDNO介导的反应。雌激素的有益作用在接受L-NAME治疗的兔子中持续存在，这表明17β-雌二醇的抗动脉粥样硬化作用也涉及不依赖一氧化氮的机制。任何一种治疗均未改变血清胆固醇水平。在这些条件下，17β-雌二醇治疗也显著增加了EDNO的产生。17β-雌二醇使斑块大小减小总是伴随着EDNO产生增加，表明这两个事件之间存在密切关联。结果表明，即使在患有严重内皮功能障碍的患者中，雌激素治疗也可能对动脉粥样硬化起到保护作用。
