17beta-estradiol decreases endothelin-1 levels in the coronary circulation of postmenopausal women with coronary artery disease.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Webb
C M
CM
Cardiac Medicine, National Heart & Lung Institute, Imperial College School of Medicine, and Royal Brompton Hospital, London, UK.
Ghatei
M A
MA
McNeill
J G
JG
Collins
P
P
D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000097:blood* / Q000503:physiopathology; D019332:Endothelin-1 / Q000097:blood*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010208:Papaverine / Q000494:pharmacology; D017698:Postmenopause / Q000097:blood* / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D016387:Women's Health
D019332:Endothelin-1; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013373:Substance P; D004958:Estradiol; D010208:Papaverine; D007548:Isosorbide Dinitrate