Williams J K, Delansorne R, Paris J
The Comparative Medicine Clinical Research Center, Department of Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC, USA.
J Steroid Biochem Mol Biol. 1998 Apr;65(1-6):219-24. doi: 10.1016/s0960-0760(98)00020-x.
It has been known for many years that sex hormones modulate vasodilator responses of arteries supplying the uterus with blood. Recently, it has been shown that sex hormones such as estrogen modulate vasomotor responses of other arteries, including coronary arteries. It is thought that modulation of vasodilator and constrictor responses of coronary arteries may be one mechanism by which estrogen affects the risk of coronary heart disease. Although several studies have examined the effects (and potential mechanisms) of estrogen on vasodilator responses of nonatherosclerotic arteries, few have focused on estrogen's effects on atherosclerotic coronary arteries. In studies of ovariectomized atherosclerotic female cynomolgus monkeys, both long-term (2 years) and short-term (20 min) estradiol treatment augments dilator responses to acetylcholine, but not nitroglycerin. Presumably, this indicates an effect of estradiol on endothelium-mediated dilator responses of coronary arteries. Addition of the progestin medroxyprogesterone acetate diminishes the beneficial effect of conjugated equine estrogens on these dilator responses. This is significant because a progestin is usually added to estrogen replacement to reduce the risk of endometrial and breast cancer associated with unopposed estrogen therapy. However, it would seem that not all progestins act similarly on vascular reactivity. Studies in monkeys indicate that addition of progesterone or the progestin medroxyprogesterone acetate does not diminish the beneficial effects of estrogen on coronary dilator responses. Thus it would appear that different estrogen/progestin combinations may affect vascular reactivity in different manners, There is also an effort being made to examine the potential of different kinds of estrogens on cardiovascular risk. Studies in monkeys indicate that one of the estrogens found in conjugated equine estrogens (17 alpha-dihydroequilenin) has estrogen effects on vascular reactivity without having detrimental effects on uterine pathology. The isoflavones "plant estrogens" found in soy protein also have estrogenic effects on vascular reactivity and inhibition.
多年来人们已经知道，性激素可调节为子宫供血的动脉的血管舒张反应。最近有研究表明，雌激素等性激素可调节包括冠状动脉在内的其他动脉的血管舒缩反应。据认为，调节冠状动脉的血管舒张和收缩反应可能是雌激素影响冠心病风险的一种机制。尽管有几项研究探讨了雌激素对非动脉粥样硬化动脉血管舒张反应的影响（以及潜在机制），但很少有研究关注雌激素对动脉粥样硬化冠状动脉的影响。在对去卵巢的动脉粥样硬化雌性食蟹猴的研究中，长期（2年）和短期（20分钟）雌二醇治疗均可增强对乙酰胆碱的舒张反应，但对硝酸甘油则无此作用。据推测，这表明雌二醇对冠状动脉内皮介导的舒张反应有影响。添加孕激素醋酸甲羟孕酮会减弱结合型马雌激素对这些舒张反应的有益作用。这一点很重要，因为通常会在雌激素替代治疗中添加孕激素，以降低与无对抗雌激素治疗相关的子宫内膜癌和乳腺癌风险。然而，似乎并非所有孕激素对血管反应性的作用都相似。对猴子的研究表明，添加孕酮或孕激素醋酸甲羟孕酮不会减弱雌激素对冠状动脉舒张反应的有益作用。因此，不同的雌激素/孕激素组合可能以不同方式影响血管反应性。人们也在努力研究不同种类雌激素对心血管风险的潜在影响。对猴子的研究表明，结合型马雌激素中发现的一种雌激素（17α-二氢马萘雌酮）对血管反应性有雌激素作用，而对子宫病理无不良影响。大豆蛋白中的异黄酮“植物雌激素”对血管反应性和抑制也有雌激素作用。
