Williams J K, Honoré E K, Washburn S A, Clarkson T B
Comparative Medicine Clinical Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1040.
J Am Coll Cardiol. 1994 Dec;24(7):1757-61. doi: 10.1016/0735-1097(94)90184-8.
We attempted to determine whether continuous and cyclic medroxyprogesterone acetate modulates the effects of estrogen on dilation of atherosclerotic coronary arteries in surgically postmenopausal female monkeys.
Estrogen replacement in postmenopausal women preserves normal dilator responses of atherosclerotic coronary arteries. The effects of progestins on coronary artery reactivity have not been determined.
Repeated quantitative coronary angiography was used to study the effects after 1 month of 1) no hormone replacement (control) or oral administration of 2) continuous conjugated equine estrogens, 3) cyclic high dose medroxyprogesterone acetate (MPA) given on days 16 to 26 of the month, 4) conjugated equine estrogens plus continuous low dose MPA, or 5) conjugated equine estrogens plus cyclic high dose MPA on endothelium-mediated dilation of atherosclerotic coronary arteries in 12 cynomolgus monkeys. Change in diameter of the left circumflex coronary artery was measured in response to intracoronary infusions of acetylcholine (10(-6) mol/liter per min) and nitroglycerin (15 micrograms/min).
Coronary arteries constricted during no hormone treatment (-8 +/- 3% [mean +/- SEM]), dilated during conjugated equine estrogen treatment (+3 +/- 1%, p < 0.05 vs. control) and constricted during cyclic MPA treatment (-3 +/- 2%). Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen inhibited acetylcholine responses by 50% (p < 0.05 vs. conjugated equine estrogens). There was no effect of treatment on vascular response to nitroglycerin (p > 0.05).
Treatment with conjugated equine estrogens, but not MPA, augmented endothelium-mediated dilation of atherosclerotic coronary arteries. Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen diminished endothelium-mediated dilation.
我们试图确定持续和周期性醋酸甲羟孕酮是否会调节雌激素对手术绝经后雌性猴子动脉粥样硬化冠状动脉扩张的影响。
绝经后女性进行雌激素替代可维持动脉粥样硬化冠状动脉的正常扩张反应。孕激素对冠状动脉反应性的影响尚未确定。
采用重复定量冠状动脉造影术，研究12只食蟹猴在1个月后，1）不进行激素替代（对照）或口服2）持续结合马雌激素、3）在每月第16至26天给予周期性高剂量醋酸甲羟孕酮（MPA）、4）结合马雌激素加持续低剂量MPA，或5）结合马雌激素加周期性高剂量MPA对动脉粥样硬化冠状动脉内皮介导扩张的影响。通过冠状动脉内注入乙酰胆碱（每分钟10(-6)摩尔/升）和硝酸甘油（每分钟15微克）来测量左旋冠状动脉直径的变化。
在无激素治疗期间冠状动脉收缩（-8±3%[平均值±标准误]），在结合马雌激素治疗期间扩张（+3±1%，与对照相比p<0.05），在周期性MPA治疗期间收缩（-3±2%）。在结合马雌激素方案中添加周期性或持续性MPA可使乙酰胆碱反应抑制50%（与结合马雌激素相比p<0.05）。治疗对血管对硝酸甘油的反应没有影响（p>0.05）。
结合马雌激素治疗可增强动脉粥样硬化冠状动脉的内皮介导扩张，而MPA则无此作用。在结合马雌激素方案中添加周期性或持续性MPA会减弱内皮介导的扩张。
