17 beta-estradiol decreases endothelin-l levels in the coronary circulation of postmenopausal women with coronary artery disease

Background-Estrogen reverses acetylcholine-induced coronary vasoconstrictio n via the possible facilitation of endothelium-derived NO. Estrogen also af fects endothelium-derived constrictor factors. We therefore investigated th e effects of 17 beta-estradiol on coronary vasomotor responses to substance P (SP), and coronary sinus endothelin-1 and NO metabolite levels in postme nopausal women with coronary heart disease. Methods and Results-We studied 20 women, 14 received estrogen (mean age 65/-2 years) and 6 served as ethanol control subjects (age 63+/-3 years). Int racoronary infusions of papaverine (8 mg) and SP were administered before a nd 20 minutes after 50 pg/min 17 beta-estradiol or 0.2 mu L/min control. Co ronary blood flow was calculated from the diameter, as measured with quanti tative coronary angiography, and flow velocity, as measured with intracoron ary Doppler. Coronary sinus plasma endothelin-l and nitrite/nitrate (NO2/NO 3) were measured at baseline, at peak velocity response to each infusion, a nd every 5 minutes during the estradiol infusion. Endothelin-l levels were decreased after 20 minutes of estradiol (1.12+/-0.18 versus 0.86+/-0.17 pmo l/L baseline2 versus estradiol, P=0.05). Endothelin-1 levels to SP decrease d after 17 beta-estradiol (1.29+/-0.18 versus 1.04+/-0.15 and 1.3+/-0.16 ve rsus 0.99+/-0.17 pmol/L for before versus after estradiol, 10 and 25 pmol/m in SP; both P<0.05). NO2/NO3 levels did not change. There was no change in vasomotor responses to estradiol alone or to papaverine or SP before versus after estradiol. Conclusions-Short-term intracoronary 17 beta-estradiol administration decre ases coronary endothelin-1 levels. There was no enhancement of vasomotor re sponses to SP after the administration of estrogen, suggesting that the eff ects of estrogen on coronary acetylcholine responses may be a specific and not a generalized effect on coronary vasoreactivity.