(Circulation. 1995;92:24-30.)
© 1995 American Heart Association, Inc.
Articles |
17ß-Estradiol Attenuates Acetylcholine-Induced Coronary Arterial Constriction in Women but Not Men With Coronary Heart Disease
From the National Heart and Lung Institute and Royal Brompton National Heart and Lung Hospital, London, UK; Yale University School of Medicine, New Haven, Conn (P.M.S.); and Novo Nordisk, Bagsvaerd, Denmark (L.U.).
Correspondence to Dr Peter Collins, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK.
Background Women are protected from coronary artery disease until the menopause. Ovarian hormones are vasoactive substances that influence both hemodynamic parameters and atheroma formation. Intravenous ethinyl estradiol has been shown to reverse acetylcholine-induced vasoconstriction in cynomolgus monkeys and humans, and 17ß-estradiol improves exercise-induced myocardial ischemia in female patients. We investigated the effect of the naturally occurring estrogen 17ß-estradiol on the coronary circulation in postmenopausal women and men with coronary artery disease.
Methods and Results We studied nine postmenopausal women 59±3 years old, mean±SEM, and seven men 52±4 years old with proven coronary artery disease. They underwent measurement of coronary artery diameter and coronary blood flow after intracoronary infusion of acetylcholine 1.6 and 16 µg/min before and 20 minutes after intracoronary administration of 2.5 µg of 17ß-estradiol into atherosclerotic, nonstenotic coronary arteries. Changes in coronary artery diameter were measured by quantitative angiography, and changes in coronary blood flow were measured with an intracoronary Doppler catheter. In female patients, acetylcholine 1.6 and 16 µg/min caused constriction before the administration of 17ß-estradiol (-6±2% and -8±5%, respectively, compared with baseline). This constrictor response was converted to dilatation after intracoronary administration of 17ß-estradiol (+8±2% and +9±3%, respectively; P<.01 before versus after estrogen). Acetylcholine 1.6 and 16 µg/min increased coronary blood flow before and after the infusion of 17ß-estradiol. However, the mean acetylcholine-induced increases in coronary flow were significantly greater (P<.009) after (126±37% and 248±89%, respectively) than before (94±31% and 143±49% mL/min, respectively) the administration of 17ß-estradiol. 17ß-Estradiol alone had no significant effect on coronary diameter or coronary blood flow (P>.05). Isosorbide dinitrate (1 mg) caused dilatation of the coronary arteries by 11±2% (P<.005). In men, acetylcholine 1.6 and 16 µg/min caused constriction both before and after the administration of 17ß-estradiol and caused similar increases in coronary blood flow both before and after the intracoronary administration of 17ß-estradiol. Infusion of intracoronary placebo in six female control patients 55±3 years old and six male control patients 56±3 years old did not change coronary diameter responses or coronary blood flow responses to acetylcholine.
Conclusions 17ß-Estradiol modulates acetylcholine-induced coronary artery responses of female but not male atherosclerotic coronary arteries in vivo. These human data confirm reports from studies in cynomolgus monkeys that estrogen modulates the responses of atherosclerotic coronary arteries. An enhancement of endothelium-dependent relaxation by natural estrogen (as used in most hormone replacement therapy) may be important in postmenopausal women with established coronary heart disease and may contribute to the acute effect of 17ß-estradiol on blood flow and its long-term protective effect on the development of coronary artery disease.
Key Words: hormones • arteries • circulation
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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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D. M. Herrington, B. L. Werbel, W. A. Riley, B. E. Pusser, and T. M. Morgan Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease J. Am. Coll. Cardiol., June 1, 1999; 33(7): 2030 - 2037. [Abstract] [Full Text] [PDF]
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G. M. C. Rosano, F. Leonardo, P. Pagnotta, F. Pelliccia, G. Panina, E. Cerquetani, P. L. della Monica, B. Bonfigli, M. Volpe, and S. L. Chierchia Acute Anti-Ischemic Effect of Testosterone in Men With Coronary Artery Disease Circulation, April 6, 1999; 99(13): 1666 - 1670. [Abstract] [Full Text] [PDF]
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H. Teoh, S. W.S. Leung, and R. Y.K. Man Short-term exposure to physiological levels of 17{beta}-estradiol enhances endothelium-independent relaxation in porcine coronary artery Cardiovasc Res, April 1, 1999; 42(1): 224 - 231. [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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 L. A. Stephenson and M. A. Kolka Esophageal temperature threshold for sweating decreases before ovulation in premenopausal women J Appl Physiol, January 1, 1999; 86(1): 22 - 28. [Abstract] [Full Text] [PDF]
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W. H. Kaesemeyer, R. B. Caldwell, J. Huang, and R. W. Caldwell Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions J. Am. Coll. Cardiol., January 1, 1999; 33(1): 234 - 241. [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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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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 J. K. Liao Endothelium and acute coronary syndromes Clin. Chem., August 1, 1998; 44(8): 1799 - 1808. [Abstract] [Full Text] [PDF]
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H. T. Westerveld, J. E. R. van Lennep, H. W. O. R. van Lennep, A.-H. Liem, J. A. J. de Boo, Y. T. van der Schouw, and D. W. Erkelens Apolipoprotein B and Coronary Artery Disease in Women : A Cross-sectional Study in Women Undergoing Their First Coronary Angiography Arterioscler Thromb Vasc Biol, July 1, 1998; 18(7): 1101 - 1107. [Abstract] [Full Text] [PDF]
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M. Kahonen, J.-P. Tolvanen, K. Sallinen, X. Wu, and I. Porsti Influence of gender on control of arterial tone in experimental hypertension Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H15 - H22. [Abstract] [Full Text] [PDF]
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Y. Nakano, T. Oshima, H. Matsuura, G. Kajiyama, and M. Kambe Effect of 17ß-Estradiol on Inhibition of Platelet Aggregation In Vitro Is Mediated by an Increase in NO Synthesis Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 961 - 967. [Abstract] [Full Text] [PDF]
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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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L. A. Fitzpatrick and M. D. Editorial: Coronary Artery Disease in Women--an Equal Opportunity Killer J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 719 - 720. [Full Text]
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P. J. Nestel, T. Yamashita, T. Sasahara, S. Pomeroy, A. Dart, P. Komesaroff, A. Owen, and M. Abbey Soy Isoflavones Improve Systemic Arterial Compliance but Not Plasma Lipids in Menopausal and Perimenopausal Women Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3392 - 3398. [Abstract] [Full Text]
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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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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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B. Bruck, U. Brehme, N. Gugel, S. Hanke, G. Finking, C. Lutz, N. Benda, F. W. Schmahl, R. Haasis, and H. Hanke Gender-Specific Differences in the Effects of Testosterone and Estrogen on the Development of Atherosclerosis in Rabbits Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2192 - 2199. [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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N. H. Bjarnason, J. Haarbo, I. Byrjalsen, R. F. Kauffman, and C. Christiansen Raloxifene Inhibits Aortic Accumulation of Cholesterol in Ovariectomized, Cholesterol-Fed Rabbits Circulation, September 16, 1997; 96(6): 1964 - 1969. [Abstract] [Full Text]
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S. Oparil, R. L. Levine, S.-J. Chen, J. Durand, and Y.F. Chen Sexually Dimorphic Response of the Balloon-Injured Rat Carotid Artery to Hormone Treatment Circulation, March 4, 1997; 95(5): 1301 - 1307. [Abstract] [Full Text]
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H. Schunkert, A.H. J. Danser, H.-W. Hense, F. H.M. Derkx, S. Kurzinger, and G. A.J. Riegger Effects of Estrogen Replacement Therapy on the Renin-Angiotensin System in Postmenopausal Women Circulation, January 7, 1997; 95(1): 39 - 45. [Abstract] [Full Text]
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E. Barrett-Connor Sex Differences in Coronary Heart Disease: Why Are Women So Superior? The 1995 Ancel Keys Lecture Circulation, January 7, 1997; 95(1): 252 - 264. [Full Text]
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Y. D. Kim, B. Chen, J. Beauregard, P. Kouretas, G. Thomas, M. Y. Farhat, A. K. Myers, and D. E. Lees 17ß-Estradiol Prevents Dysfunction of Canine Coronary Endothelium and Myocardium and Reperfusion Arrhythmias After Brief Ischemia/Reperfusion Circulation, December 1, 1996; 94(11): 2901 - 2908. [Abstract] [Full Text]
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