Zhang Y, Davidge S T
Perinatal Research Centre, Departments of Ob/Gyn and Physiology, University of Alberta, Edmonton, Alberta, Canada.
Hypertension. 1999 Nov;34(5):1117-22. doi: 10.1161/01.hyp.34.5.1117.
Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression and/or activity and that nitric oxide may play a role in attenuating vasoconstrictor responses. Yet there are still controversies in this field. Our hypothesis was that the role of nitric oxide in modulating vasoconstrictor responses in estrogen-replaced animals depends on the agonist. The aim of the study was to determine the effect of long-term estrogen replacement on vascular reactivity of resistance-sized mesenteric arteries in ovariectomized rats with the use of a variety of vasoconstrictors. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. 17beta-estradiol pellets (0.5 mg/pellet) were implanted in the estrogen-replaced group (n=9) for 4 weeks; placebo pellets were used in the ovariectomized group (n=10). Resistance-sized mesenteric arteries were dissected and mounted onto a dual-chamber arteriograph system. Estradiol replacement did not alter the response of mesenteric arteries to either arginine vasopressin or the thromboxane mimetic U46619. Inhibition of nitric oxide synthase with N(G)-monomethyl-L-arginine (100 micromol/L) did not modulate these vasoconstrictor responses in either group of rats. In contrast, the dose-response curve of the adrenergic agonist phenylephrine was significantly attenuated for the estradiol-replaced rats compared with the ovariectomized group (EC(50)=0.90+/-0.17 vs 0.44+/-0.08 micromol/L, P<0.05). After incubation with N(G)-monomethyl-L-arginine, the EC(50) of phenylephrine significantly decreased in both groups, but a significant difference remained between the 2 groups (EC(50)=0.41+/-0.08 vs 0.28+/-0.02 micromol/L, P<0.05). Importantly, Western immunoblotting demonstrated that the expression of alpha(1)-adrenergic receptors was significantly suppressed by estradiol replacement. We conclude that estrogen may have a specific effect on adrenergic vasoconstriction by modulating its receptors.
近期研究表明，雌激素可增加内皮型一氧化氮合酶的表达和/或活性，且一氧化氮可能在减弱血管收缩反应中发挥作用。然而，该领域仍存在争议。我们的假设是，一氧化氮在调节雌激素替代动物血管收缩反应中的作用取决于激动剂。本研究的目的是利用多种血管收缩剂，确定长期雌激素替代对去卵巢大鼠阻力型肠系膜动脉血管反应性的影响。11周龄的雌性斯普拉-道利大鼠接受去卵巢手术。雌激素替代组（n = 9）植入17β-雌二醇丸（每丸0.5毫克），持续4周；去卵巢组（n = 10）使用安慰剂丸。解剖阻力型肠系膜动脉并安装到双腔动脉造影系统上。雌二醇替代并未改变肠系膜动脉对精氨酸加压素或血栓素类似物U46619的反应。用N(G)-单甲基-L-精氨酸（100微摩尔/升）抑制一氧化氮合酶，在两组大鼠中均未调节这些血管收缩反应。相比之下，与去卵巢组相比，雌激素替代大鼠的肾上腺素能激动剂去氧肾上腺素的剂量-反应曲线明显减弱（半数有效浓度[EC(50)] = 0.90±0.17对0.44±0.08微摩尔/升，P<0.05）。用N(G)-单甲基-L-精氨酸孵育后，两组去氧肾上腺素的EC(50)均显著降低，但两组之间仍存在显著差异（EC(50)=0.41±0.08对0.28±0.02微摩尔/升，P<0.05）。重要的是，蛋白质免疫印迹法表明，雌二醇替代显著抑制了α(1)-肾上腺素能受体的表达。我们得出结论，雌激素可能通过调节其受体对肾上腺素能血管收缩产生特定作用。
