Collins P, Shay J, Jiang C, Moss J
Department of Cardiac Medicine, University of London, England.
Circulation. 1994 Oct;90(4):1964-8. doi: 10.1161/01.cir.90.4.1964.
Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women, and estrogen treatment modulates endothelium-dependent vasodilation in ovariectomized, atherosclerotic monkeys. Estradiol-17 beta also induces relaxation in isolated rabbit coronary arteries as well as cerebral basilar arteries. The estrogen concentrations required to induce such relaxation are in the pharmacological range (10(-6) to 10(-5) mol/L).
The present study was designed to test whether the sensitivity and specificity of the relaxing response of coronary vascular smooth muscle to exogenous estradiol-17 beta is dependent on the sex hormone status of the animal. In coronary artery rings contracted with PGF2 alpha (3 x 10(-5) mol/L), estradiol-17 beta caused significant relaxation at a physiological estrogen concentration (10(-9) mol/L), in coronary artery rings from oophorectomized, estrogen-treated and acutely estrogen-withdrawn rabbits only. Relaxation induced by estradiol-17 beta at lower concentrations (10(-9) to 10(-6) mol/L) in these rings was 20 +/- 6%, 42 +/- 8%, 54 +/- 9%, and 75 +/- 8%, respectively, compared with 4 +/- 2%, 12 +/- 5%, 16 +/- 7%, and 25 +/- 12% and 5 +/- 2%, 12 +/- 5%, 18 +/- 8%, and 23 +/- 10% in rings from estrogen-maintained and oophorectomized rabbits, respectively (P < .01). The relaxation in coronary artery rings from estrogen-treated and acutely estrogen-withdrawn rabbits was endothelium and nitric oxide dependent since it was abolished by endothelium removal and the nitric oxide synthase inhibitor N omega-nitro-L-arginine.
This study demonstrates that estrogen-induced, endothelium-dependent relaxation of coronary arteries may, in some species, depend on the sex hormone status of the animal. These findings may help to better understand the effects of ovarian steroids in the coronary circulation of females.
雌激素替代疗法可降低绝经后女性患冠心病的风险，雌激素治疗可调节去卵巢、动脉粥样硬化猴子的内皮依赖性血管舒张。17β-雌二醇还可诱导离体兔冠状动脉以及脑基底动脉舒张。诱导这种舒张所需的雌激素浓度处于药理范围（10⁻⁶至10⁻⁵mol/L）。
本研究旨在测试冠状动脉血管平滑肌对外源性17β-雌二醇舒张反应的敏感性和特异性是否取决于动物的性激素状态。在与PGF2α（3×10⁻⁵mol/L）收缩的冠状动脉环中，17β-雌二醇仅在生理雌激素浓度（10⁻⁹mol/L）时，在去卵巢、接受雌激素治疗以及急性撤去雌激素的兔子的冠状动脉环中引起显著舒张。在这些环中，17β-雌二醇在较低浓度（10⁻⁹至10⁻⁶mol/L）时诱导的舒张分别为20±6%、42±8%、54±9%和75±8%，而在雌激素维持状态和去卵巢兔子的环中分别为4±2%、12±5%、16±7%和25±12%以及5±2%、12±5%、18±8%和23±10%（P<.01）。来自接受雌激素治疗和急性撤去雌激素兔子的冠状动脉环中的舒张是内皮和一氧化氮依赖性的，因为去除内皮和一氧化氮合酶抑制剂Nω-硝基-L-精氨酸可消除这种舒张。
本研究表明，雌激素诱导的冠状动脉内皮依赖性舒张在某些物种中可能取决于动物的性激素状态。这些发现可能有助于更好地理解卵巢类固醇在女性冠状动脉循环中的作用。
