Webb C M, Ghatei M A, McNeill J G, Collins P
Cardiac Medicine, National Heart & Lung Institute, Imperial College School of Medicine, and Royal Brompton Hospital, London, UK.
Circulation. 2000 Oct 3;102(14):1617-22. doi: 10.1161/01.cir.102.14.1617.
Estrogen reverses acetylcholine-induced coronary vasoconstriction via the possible facilitation of endothelium-derived NO. Estrogen also affects endothelium-derived constrictor factors. We therefore investigated the effects of 17beta-estradiol on coronary vasomotor responses to substance P (SP), and coronary sinus endothelin-1 and NO metabolite levels in postmenopausal women with coronary heart disease.
We studied 20 women; 14 received estrogen (mean age 65+/-2 years) and 6 served as ethanol control subjects (age 63+/-3 years). Intracoronary infusions of papaverine (8 mg) and SP were administered before and 20 minutes after 50 pg/min 17beta-estradiol or 0.2 microL/min control. Coronary blood flow was calculated from the diameter, as measured with quantitative coronary angiography, and flow velocity, as measured with intracoronary Doppler. Coronary sinus plasma endothelin-1 and nitrite/nitrate (NO(2)/NO(3)) were measured at baseline, at peak velocity response to each infusion, and every 5 minutes during the estradiol infusion. Endothelin-1 levels were decreased after 20 minutes of estradiol (1.12+/-0.18 versus 0.86+/-0.17 pmol/L baseline2 versus estradiol, P:=0.05). Endothelin-1 levels to SP decreased after 17beta-estradiol (1.29+/-0. 18 versus 1.04+/-0.15 and 1.3+/-0.16 versus 0.99+/-0.17 pmol/L for before versus after estradiol, 10 and 25 pmol/min SP; both P:<0.05). NO(2)/NO(3) levels did not change. There was no change in vasomotor responses to estradiol alone or to papaverine or SP before versus after estradiol.
Short-term intracoronary 17beta-estradiol administration decreases coronary endothelin-1 levels. There was no enhancement of vasomotor responses to SP after the administration of estrogen, suggesting that the effects of estrogen on coronary acetylcholine responses may be a specific and not a generalized effect on coronary vasoreactivity.
雌激素可能通过促进内皮源性一氧化氮（NO）的生成来逆转乙酰胆碱诱导的冠状动脉收缩。雌激素还会影响内皮源性收缩因子。因此，我们研究了17β-雌二醇对冠心病绝经后女性冠状动脉对P物质（SP）的血管舒缩反应以及冠状窦内皮素-1和NO代谢产物水平的影响。
我们研究了20名女性；14名接受雌激素治疗（平均年龄65±2岁），6名作为乙醇对照受试者（年龄63±3岁）。在以50 pg/min的速度输注17β-雌二醇或0.2 μL/min的对照液之前及之后20分钟，分别进行冠状动脉内注射罂粟碱（8 mg）和SP。通过定量冠状动脉造影测量的直径以及冠状动脉内多普勒测量的流速来计算冠状动脉血流量。在基线、对每次注射的峰值速度反应时以及雌二醇输注期间每5分钟测量一次冠状窦血浆内皮素-1和亚硝酸盐/硝酸盐（NO₂/NO₃）。雌二醇输注20分钟后内皮素-1水平降低（基线时为1.12±0.18 pmol/L，与雌二醇后为0.86±0.17 pmol/L相比，P = 0.05）。17β-雌二醇后对SP的内皮素-1水平降低（对于雌二醇前与雌二醇后，10和25 pmol/min的SP，分别为1.29±0.18与1.04±0.15以及1.3±0.16与0.99±0.17 pmol/L；两者P < 0.05）。NO₂/NO₃水平未改变。单独对雌二醇或对雌二醇前后的罂粟碱或SP的血管舒缩反应没有变化。
短期冠状动脉内给予17β-雌二醇可降低冠状动脉内皮素-1水平。雌激素给药后对SP的血管舒缩反应没有增强，这表明雌激素对冠状动脉乙酰胆碱反应的影响可能是对冠状动脉血管反应性的一种特异性而非普遍作用。
