Circulation, Vol 89, 52-60, Copyright © 1994 by American Heart Association
SE Reis, ST Gloth, RS Blumenthal, JR Resar, HA Zacur, G Gerstenblith and JA Brinker
BACKGROUND: Estrogen administration in postmenopausal women is associated
with a 50% reduction in the clinical manifestations of coronary artery
disease. The mechanisms are not known, although one potential explanation
is estrogen-induced modulation of coronary vasoreactivity. Acetylcholine is
an endothelium-dependent vasodilator that may be used to assess coronary
vasoreactivity and elicits coronary responses that parallel those found
with common daily vasomotor stimuli. Therefore, we tested whether estrogen
attenuates abnormal coronary vasomotor responses to acetylcholine in
postmenopausal women. METHODS AND RESULTS: Acetylcholine-induced changes in
coronary flow, resistance, and cross-sectional area were determined before
and 15 minutes after intravenous administration of ethinyl estradiol (EE,
35 micrograms) in 15 postmenopausal women. The influence of estrogen on
basal coronary flow, resistance, and epicardial cross-sectional area was
also assessed by measuring these parameters before and after EE or placebo
administration in 33 women. Estrogen altered basal coronary vasomotor tone
in 22 women as manifested by an EE-induced 23.3 +/- 4.5% (mean +/- SEM)
increase (P < .01) in coronary flow, a 15.0 +/- 3.2% decrease (P <
.01) in resistance, and a 20.0 +/- 6.5% increase (P = .02) in epicardial
cross-sectional area. Placebo administration in 11 women did not change
these parameters. Estrogen also attenuated abnormal coronary vasomotor
responses to acetylcholine. Seven women who exhibited a paradoxical
acetylcholine-induced decrease in coronary flow (-33.5 +/- 12.3%, P <
.01) and increase in resistance (38.9 +/- 14.1%, P = .05) and seven who had
an abnormal acetylcholine-induced decrease in epicardial cross-sectional
area (-14.2 +/- 4.4%; P = .04) did not have acetylcholine-induced changes
in these parameters after EE administration. Acetylcholine-induced flow,
resistance, and cross- sectional area responses before and after EE were
significantly different (P < .01, P = .02, and P = .02, respectively).
Normal coronary responses to acetylcholine were not affected by EE
administration. CONCLUSIONS: EE attenuates abnormal coronary vasomotor
responses to acetylcholine in postmenopausal women. EE also decreases basal
coronary vasomotor tone as manifested by increased coronary flow, decreased
resistance, and increased epicardial cross-sectional area. These acute
effects of estrogen on coronary vasoreactivity may explain, in part, the
cardioprotective effects of estrogen in postmenopausal women.
ARTICLES
Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women
Department of Medicine, Johns Hopkins University, Baltimore, Md.
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N. F. Col, S. G. Pauker, R. J. Goldberg, M. H. Eckman, R. K. Orr, E. M. Ross, and J. B. Wong Individualizing Therapy to Prevent Long-term Consequences of Estrogen Deficiency in Postmenopausal Women Arch Intern Med, July 12, 1999; 159(13): 1458 - 1466. [Abstract] [Full Text] [PDF]
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 M. E. Mendelsohn and R. H. Karas The Protective Effects of Estrogen on the Cardiovascular System N. Engl. J. Med., June 10, 1999; 340(23): 1801 - 1811. [Full Text] [PDF]
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 V M Miller Gender and vascular reactivity Lupus, June 1, 1999; 8(5): 409 - 415. [Abstract] [PDF]
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C. N. B. Merz The Efficacy of Hormonal Therapy for Reducing Coronary Artery Disease in Women J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1810 - 1812. [Full Text]
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C. N. Bairey Merz, S. F. Kelsey, C. J. Pepine, N. Reichek, S. E. Reis, W. J. Rogers, B. L. Sharaf, G. Sopko, and for the WISE Study Group The Women's Ischemia Syndrome Evaluation (WISE) Study: protocol design, methodology and feasibility report J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1453 - 1461. [Abstract] [Full Text] [PDF]
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R. M. Goetz, H. S. Thatte, P. Prabhakar, M. R. Cho, T. Michel, and D. E. Golan Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase PNAS, March 16, 1999; 96(6): 2788 - 2793. [Abstract] [Full Text] [PDF]
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I. Dorup, K. Skajaa, and K. E. Sorensen Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H821 - H825. [Abstract] [Full Text] [PDF]
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R.-T. Chang, G. P. Lambert, P. L. Moseley, F. K. Chapler, and C. V. Gisolfi Effect of estrogen supplementation on exercise thermoregulation in premenopausal women J Appl Physiol, December 1, 1998; 85(6): 2082 - 2088. [Abstract] [Full Text] [PDF]
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 A. Huang, D. Sun, A. Koller, and G. Kaley Gender difference in flow-induced dilation and regulation of shear stress: role of estrogen and nitric oxide Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1571 - R1577. [Abstract] [Full Text] [PDF]
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G. Schillaci, P. Verdecchia, C. Borgioni, A. Ciucci, and C. Porcellati Early Cardiac Changes After Menopause Hypertension, October 1, 1998; 32(4): 764 - 769. [Abstract] [Full Text] [PDF]
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M. Gerhard, B. W. Walsh, A. Tawakol, E. A. Haley, S. J. Creager, E. W. Seely, P. Ganz, and M. A. Creager Estradiol Therapy Combined With Progesterone and Endothelium-Dependent Vasodilation in Postmenopausal Women Circulation, September 22, 1998; 98(12): 1158 - 1163. [Abstract] [Full Text] [PDF]
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 G. I. Gorodeski, T. Yang, M. N. Levy, J. Goldfarb, and W. H. Utian Modulation of Coronary Vascular Resistance in Female Rabbits by Estrogen and Progesterone Reproductive Sciences, July 1, 1998; 5(4): 197 - 202. [Abstract] [PDF]
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P. A. Komesaroff, C. V.S. Black, and R. A. Westerman A Novel, Nongenomic Action of Estrogen on the Cardiovascular System J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2313 - 2316. [Abstract] [Full Text]
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A. A. Nekooeian and C. C. Y. Pang Estrogen restores role of basal nitric oxide in control of vascular tone in rats with chronic heart failure Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H2094 - H2099. [Abstract] [Full Text] [PDF]
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M. Matteis, E. Troisi, B. C. Monaldo, C. Caltagirone, and M. Silvestrini Age and Sex Differences in Cerebral Hemodynamics : A Transcranial Doppler Study Stroke, May 1, 1998; 29(5): 963 - 967. [Abstract] [Full Text] [PDF]
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R. A. Vogel and M. C. Corretti Estrogens, Progestins, and Heart Disease : Can Endothelial Function Divine the Benefit? Circulation, April 7, 1998; 97(13): 1223 - 1226. [Full Text] [PDF]
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A. Nitenberg, F. Paycha, S. Ledoux, R. Sachs, J.-R. Attali, and P. Valensi Coronary Artery Responses to Physiological Stimuli Are Improved by Deferoxamine but not by L-Arginine in Non–Insulin-Dependent Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Risk Factors Circulation, March 3, 1998; 97(8): 736 - 743. [Abstract] [Full Text] [PDF]
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J. Binko and H. Majewski 17beta -Estradiol reduces vasoconstriction in endothelium-denuded rat aortas through inducible NOS Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H853 - H859. [Abstract] [Full Text] [PDF]
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R. D. Minshall, F. Z. Stanczyk, K. Miyagawa, B. Uchida, M. Axthelm, M. Novy, and K. Hermsmeyer Ovarian Steroid Protection against Coronary Artery Hyperreactivity in Rhesus Monkeys J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 649 - 659. [Abstract] [Full Text]
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S. E. Reis, V. Bhoopalam, K. A. Zell, P. J. Counihan, A. J. C. Smith, S. Pham, and S. Murali Conjugated Estrogens Acutely Abolish Abnormal Cold-Induced Coronary Vasoconstriction in Male Cardiac Allografts Circulation, January 13, 1998; 97(1): 23 - 25. [Abstract] [Full Text] [PDF]
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T. Caulin-Glaser, G. Garcia-Cardena, P. Sarrel, W. C. Sessa, and J. R. Bender 17ß-Estradiol Regulation of Human Endothelial Cell Basal Nitric Oxide Release, Independent of Cytosolic Ca2+ Mobilization Circ. Res., November 19, 1997; 81(5): 885 - 892. [Abstract] [Full Text]
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K. Sudhir, T. M. Chou, K. Chatterjee, E. P. Smith, T. C. Williams, J. P. Kane, M. J. Malloy, K. S. Korach, and G. M. Rubanyi Premature Coronary Artery Disease Associated With a Disruptive Mutation in the Estrogen Receptor Gene in a Man Circulation, November 18, 1997; 96(10): 3774 - 3777. [Abstract] [Full Text]
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V. Guetta, A. A. Quyyumi, A. Prasad, J. A. Panza, M. Waclawiw, and R. O. Cannon III The Role of Nitric Oxide in Coronary Vascular Effects of Estrogen in Postmenopausal Women Circulation, November 4, 1997; 96(9): 2795 - 2801. [Abstract] [Full Text]
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G. M.C. Rosano, A. M. Caixeta, S. Chierchia, S. Arie, M. Lopez-Hidalgo, W. I. Pereira, F. Leonardo, C. M. Webb, F. Pileggi, and P. Collins Short-term Anti-Ischemic Effect of 17ß-Estradiol in Postmenopausal Women With Coronary Artery Disease Circulation, November 4, 1997; 96(9): 2837 - 2841. [Abstract] [Full Text]
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D. A. Barber and V. M. Miller Gender differences in endothelium-dependent relaxations do not involve NO in porcine coronary arteries Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2325 - H2332. [Abstract] [Full Text] [PDF]
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S. M. Herman, J. T.C. Robinson, R. J. McCredie, M. R. Adams, M. J. Boyer, and D. S. Celermajer Androgen Deprivation Is Associated With Enhanced Endothelium-Dependent Dilatation in Adult Men Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2004 - 2009. [Abstract] [Full Text]
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K. A. Roberts, M. M. Woo, and J. C. Rutledge Nitric Oxide Mediates LDL Uptake in the Artery Wall in Response to High Concentrations of 17ß-Estradiol Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2123 - 2131. [Abstract] [Full Text]
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T. Akasaka, K. Yoshida, A. Yamamuro, T. Hozumi, T. Takagi, S. Morioka, and J. Yoshikawa Phasic Coronary Flow Characteristics in Patients With Constrictive Pericarditis : Comparison With Restrictive Cardiomyopathy Circulation, September 16, 1997; 96(6): 1874 - 1881. [Abstract] [Full Text]
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J. K. Williams, E. K. Honore, and M. R. Adams Contrasting Effects of Conjugated Estrogens and Tamoxifen on Dilator Responses of Atherosclerotic Epicardial Coronary Arteries in Nonhuman Primates Circulation, September 16, 1997; 96(6): 1970 - 1975. [Abstract] [Full Text]
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C. R. White, J. Shelton, S.-J. Chen, V. Darley-Usmar, L. Allen, C. Nabors, P. W. Sanders, Y.-F. Chen, and S. Oparil Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury Circulation, September 2, 1997; 96(5): 1624 - 1630. [Abstract] [Full Text]
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A. D. Freay, S. W. Curtis, K. S. Korach, and G. M. Rubanyi Mechanism of Vascular Smooth Muscle Relaxation by Estrogen in Depolarized Rat and Mouse Aorta : Role of Nuclear Estrogen Receptor and Ca2+ Uptake Circ. Res., August 19, 1997; 81(2): 242 - 248. [Abstract] [Full Text]
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E. M. Brooks, A. L. Morgan, J. M. Pierzga, S. L. Wladkowski, J. T. O'Gorman, J. A. Derr, and W. L. Kenney Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women J Appl Physiol, August 1, 1997; 83(2): 477 - 484. [Abstract] [Full Text] [PDF]
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P. Holm, S. Stender, H. o. Andersen, B. F. Hansen, and B. G. Nordestgaard Antiatherogenic Effect of Estrogen Abolished by Balloon Catheter Injury in Cholesterol-Clamped Rabbits Arterioscler Thromb Vasc Biol, August 1, 1997; 17(8): 1504 - 1511. [Abstract] [Full Text]
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