Collins P, Rosano G M, Sarrel P M, Ulrich L, Adamopoulos S, Beale C M, McNeill J G, Poole-Wilson P A
National Heart and Lung Institute, National Heart and Lung Hospital, London, UK.
Circulation. 1995 Jul 1;92(1):24-30. doi: 10.1161/01.cir.92.1.24.
Women are protected from coronary artery disease until the menopause. Ovarian hormones are vasoactive substances that influence both hemodynamic parameters and atheroma formation. Intravenous ethinyl estradiol has been shown to reverse acetylcholine-induced vasoconstriction in cynomolgus monkeys and humans, and 17 beta-estradiol improves exercise-induced myocardial ischemia in female patients. We investigated the effect of the naturally occurring estrogen 17 beta-estradiol on the coronary circulation in postmenopausal women and men with coronary artery disease.
We studied nine postmenopausal women 59 +/- 3 years old, mean +/- SEM, and seven men 52 +/- 4 years old with proven coronary artery disease. They underwent measurement of coronary artery diameter and coronary blood flow after intracoronary infusion of acetylcholine 1.6 and 16 micrograms/min before and 20 minutes after intracoronary administration of 2.5 micrograms of 17 beta-estradiol into atherosclerotic, nonstenotic coronary arteries. Changes in coronary artery diameter were measured by quantitative angiography, and changes in coronary blood flow were measured with an intracoronary Doppler catheter. In female patients, acetylcholine 1.6 and 16 micrograms/min caused constriction before the administration of 17 beta-estradiol (-6 +/- 2% and -8 +/- 5%, respectively, compared with baseline). This constrictor response was converted to dilatation after intracoronary administration of 17 beta-estradiol (+8 +/- 2% and +9 +/- 3%, respectively; P < .01 before versus after estrogen). Acetylcholine 1.6 and 16 micrograms/min increased coronary blood flow before and after the infusion of 17 beta-estradiol. However, the mean acetylcholine-induced increases in coronary flow were significantly greater (P < .009) after (126 +/- 37% and 248 +/- 89%, respectively) than before (94 +/- 31% and 143 +/- 49% mL/min, respectively) the administration of 17 beta-estradiol. 17 beta-Estradiol alone had no significant effect on coronary diameter or coronary blood flow (P > .05). Isosorbide dinitrate (1 mg) caused dilatation of the coronary arteries by 11 +/- 2% (P < .005). In men, acetylcholine 1.6 and 16 micrograms/min caused constriction both before and after the administration of 17 beta-estradiol and caused similar increases in coronary blood flow both before and after the intracoronary administration of 17 beta-estradiol. Infusion of intracoronary placebo in six female control patients 55 +/- 3 years old and six male control patients 56 +/- 3 years old did not change coronary diameter responses or coronary blood flow responses to acetylcholine.
17 beta-Estradiol modulates acetylcholine-induced coronary artery responses of female but not male atherosclerotic coronary arteries in vivo. These human data confirm reports from studies in cynomolgus monkeys that estrogen modulates the responses of atherosclerotic coronary arteries. An enhancement of endothelium-dependent relaxation by natural estrogen (as used in most hormone replacement therapy) may be important in postmenopausal women with established coronary heart disease and may contribute to the acute effect of 17 beta-estradiol on blood flow and its long-term protective effect on the development of coronary artery disease.
女性在绝经前可免受冠状动脉疾病的困扰。卵巢激素是影响血液动力学参数和动脉粥样硬化形成的血管活性物质。已证实，静脉注射乙炔雌二醇可逆转食蟹猴和人类体内乙酰胆碱诱导的血管收缩，且17β - 雌二醇可改善女性患者运动诱发的心肌缺血。我们研究了天然存在的雌激素17β - 雌二醇对绝经后女性和患有冠状动脉疾病男性的冠状动脉循环的影响。
我们研究了9名平均年龄为59±3岁（均值±标准误）的绝经后女性和7名平均年龄为52±4岁且确诊患有冠状动脉疾病的男性。他们在向动脉粥样硬化、无狭窄的冠状动脉内注射2.5微克17β - 雌二醇之前及之后20分钟，分别以每分钟1.6微克和16微克的剂量冠状动脉内注射乙酰胆碱，之后测量冠状动脉直径和冠状动脉血流量。冠状动脉直径的变化通过定量血管造影测量，冠状动脉血流量的变化通过冠状动脉内多普勒导管测量。在女性患者中，在注射17β - 雌二醇之前，每分钟1.6微克和16微克的乙酰胆碱会引起血管收缩（分别比基线减少 - 6±2%和 - 8±5%）。在冠状动脉内注射17β - 雌二醇后，这种收缩反应转变为扩张（分别为 + 8±2%和 + 9±3%；雌激素注射前后比较，P <.01）。在注射17β - 雌二醇前后，每分钟1.6微克和16微克的乙酰胆碱均会增加冠状动脉血流量。然而，平均而言，乙酰胆碱诱导的冠状动脉血流量增加在注射17β - 雌二醇后（分别为126±37%和248±89%）显著大于注射前（分别为94±31%和143±49%毫升/分钟）（P <.009）。单独使用17β - 雌二醇对冠状动脉直径或冠状动脉血流量无显著影响（P >.05）。硝酸异山梨酯（1毫克）可使冠状动脉扩张11±2%（P <.005）。在男性中，每分钟1.6微克和16微克的乙酰胆碱在注射17β - 雌二醇前后均会引起血管收缩，且在冠状动脉内注射17β - 雌二醇前后引起的冠状动脉血流量增加相似。对6名平均年龄为55±3岁的女性对照患者和6名平均年龄为56±3岁的男性对照患者冠状动脉内注射安慰剂，未改变冠状动脉直径反应或对乙酰胆碱的冠状动脉血流量反应。
17β - 雌二醇在体内可调节女性而非男性动脉粥样硬化冠状动脉对乙酰胆碱的反应。这些人体数据证实了食蟹猴研究中的报告，即雌激素可调节动脉粥样硬化冠状动脉的反应。天然雌激素（大多数激素替代疗法中使用的）对内皮依赖性舒张的增强作用，对于已患有冠心病的绝经后女性可能很重要，可能有助于17β - 雌二醇对血流量的急性影响及其对冠状动脉疾病发展的长期保护作用。
