Circulation, Vol 89, 2545-2551, Copyright © 1994 by American Heart Association
DM Gilligan, AA Quyyumi and RO Cannon 3rd
BACKGROUND: Estrogen replacement therapy has been associated with a
reduction in cardiovascular events in postmenopausal women. One of the
mechanisms responsible may be a beneficial effect of estrogen on coronary
vascular function. We therefore studied the short-term effects of estrogen
on coronary artery dimensions and microvascular resistance in
postmenopausal women. METHODS AND RESULTS: Twenty postmenopausal women 61
+/- 7 years old participated in this study. Seven had angiographic evidence
of atherosclerosis of the left coronary artery. Coronary artery diameters
were measured by quantitative coronary angiography. Blood flow velocity was
measured with a Doppler wire placed in a proximal left coronary artery
segment. Left coronary artery infusions of acetylcholine (range, 10(-8) to
10(-5) mol/L estimated delivered concentrations) and of adenosine (n = 18)
and sodium nitroprusside (n = 10) were performed before and during
concomitant continuous intracoronary infusion of 17 beta-estradiol to test
endothelium-dependent and independent vasodilation, respectively.
Intracoronary infusion of estradiol increased coronary sinus estradiol
levels from postmenopausal (16 +/- 11 pg/mL) to premenopausal (282 +/- 121
pg/mL) levels. Estradiol did not affect basal coronary artery diameter,
blood flow, or resistance. Epicardial coronary artery constriction induced
by acetylcholine infusion in the control study (maximum, 10 +/- 15% from
baseline) was prevented during repeat acetylcholine infusion with
concomitant estradiol administration (P < .001). Estradiol potentiated
the vasodilator coronary microvascular response to acetylcholine as
manifest by significantly greater coronary flow (P < .001) and lower
coronary resistance (P < .02). The reduction in coronary resistance from
baseline in response to acetylcholine was significantly potentiated by
estradiol (P = .01), with a mean decrease in coronary vascular resistance
during acetylcholine infusion of 20 +/- 38% before and 35 +/- 33% during
concomitant estradiol administration. The effect of estradiol on coronary
dynamics was similar in women with and women without angiographically
apparent left coronary artery atherosclerosis and was most prominent in
women with the most impaired responses to acetylcholine at both the
epicardial (r = -.72, P < .001) and microvascular (r = -.59, P = .006)
coronary artery levels. In contrast, estradiol did not affect the coronary
epicardial or microvascular vasodilator responses to adenosine or sodium
nitroprusside. CONCLUSIONS: Physiological levels of 17 beta-estradiol
acutely and selectively potentiate endothelium-dependent vasodilation in
both large coronary conductance arteries and coronary microvasuclar
resistance arteries of postmenopausal women. This effect may contribute to
the reduction in cardiovascular events observed with estrogen replacement
therapy.
ARTICLES
Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
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A. Blum, L. Hathaway, R. Mincemoyer, W. H. Schenke, M. Kirby, G. Csako, M. A. Waclawiw, J. A. Panza, and R. O. Cannon III Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women J. Am. Coll. Cardiol., February 1, 2000; 35(2): 271 - 276. [Abstract] [Full Text] [PDF]
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F. Squadrito, D. Altavilla, G. Squadrito, A. Saitta, D. Cucinotta, L. Minutoli, B. Deodato, M. Ferlito, G. M. Campo, A. Bova, et al. Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats Cardiovasc Res, January 14, 2000; 45(2): 454 - 462. [Abstract] [Full Text] [PDF]
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A. Huang, D. Sun, A. Koller, and G. Kaley 17{beta}-Estradiol Restores Endothelial Nitric Oxide Release to Shear Stress in Arterioles of Male Hypertensive Rats Circulation, January 4, 2000; 101(1): 94 - 100. [Abstract] [Full Text] [PDF]
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 R. H. Karas, J. B. Hodgin, M. Kwoun, J. H. Krege, M. Aronovitz, W. Mackey, J. A. Gustafsson, K. S. Korach, O. Smithies, and M. E. Mendelsohn Estrogen inhibits the vascular injury response in estrogen receptor beta -deficient female mice PNAS, December 21, 1999; 96(26): 15133 - 15136. [Abstract] [Full Text] [PDF]
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G. New, S. J. Duffy, R. W. Harper, and I. T. Meredith Estrogen improves acetylcholine-induced but not metabolic vasodilation in biological males Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2341 - H2347. [Abstract] [Full Text] [PDF]
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K. K. Koh, A. Blum, L. Hathaway, R. Mincemoyer, G. Csako, M. A. Waclawiw, J. A. Panza, and R. O. Cannon III Vascular Effects of Estrogen and Vitamin E Therapies in Postmenopausal Women Circulation, November 2, 1999; 100(18): 1851 - 1857. [Abstract] [Full Text] [PDF]
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C. M. Webb, J. G. McNeill, C. S. Hayward, D. de Zeigler, and P. Collins Effects of Testosterone on Coronary Vasomotor Regulation in Men With Coronary Heart Disease Circulation, October 19, 1999; 100(16): 1690 - 1696. [Abstract] [Full Text] [PDF]
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K. Sudhir and P. A. Komesaroff Cardiovascular Actions of Estrogens in Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3411 - 3415. [Full Text] [PDF]
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E. Barrett-Connor, D. Goodman-Gruen, and B. Patay Endogenous Sex Hormones and Cognitive Function in Older Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3681 - 3685. [Abstract] [Full Text] [PDF]
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 G. B. Stefano, V. Prevot, J.-C. Beauvillain, C. Fimiani, I. Welters, P. Cadet, C. Breton, J. Pestel, M. Salzet, and T. V. Bilfinger Estradiol Coupling to Human Monocyte Nitric Oxide Release Is Dependent on Intracellular Calcium Transients: Evidence for an Estrogen Surface Receptor J. Immunol., October 1, 1999; 163(7): 3758 - 3763. [Abstract] [Full Text] [PDF]
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T. J. Anderson Assessment and treatment of endothelial dysfunction in humans J. Am. Coll. Cardiol., September 1, 1999; 34(3): 631 - 638. [Full Text] [PDF]
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I. D. Cox, H. E. Botker, J. P. Bagger, H. S. Sonne, B. O Kristensen, and J. C. Kaski Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms J. Am. Coll. Cardiol., August 1, 1999; 34(2): 455 - 460. [Abstract] [Full Text] [PDF]
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 I. Suzuma, M. Mandai, H. Takagi, K. Suzuma, A. Otani, H. Oh, K. Kobayashi, and Y. Honda 17 {beta}-Estradiol Increases VEGF Receptor-2 and Promotes DNA Synthesis in Retinal Microvascular Endothelial Cells Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 2122 - 2129. [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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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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C. A. D. Nascimento, K. Kauser, and G. M. Rubanyi Effect of 17beta -estradiol in hypercholesterolemic rabbits with severe endothelial dysfunction Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1788 - H1794. [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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P. J. Nestel, S. Pomeroy, S. Kay, P. Komesaroff, J. Behrsing, J. D. Cameron, and L. West Isoflavones from Red Clover Improve Systemic Arterial Compliance But Not Plasma Lipids in Menopausal Women J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 895 - 898. [Abstract] [Full Text]
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M.A Barbacanne, J Rami, J.B Michel, J.P Souchard, M Philippe, J.P Besombes, F Bayard, and J.F Arnal Estradiol increases rat aorta endothelium-derived relaxing factor (EDRF) activity without changes in endothelial NO synthase gene expression: possible role of decreased endothelium-derived superoxide anion production Cardiovasc Res, March 1, 1999; 41(3): 672 - 681. [Abstract] [Full Text] [PDF]
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C. Stefanadis, E. Tsiamis, J. Dernellis, and P. Toutouzas Effect of estrogen on aortic function in postmenopausal women Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H658 - H662. [Abstract] [Full Text] [PDF]
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 R. J. Gonzales and N. L. Kanagy Endothelium-Independent Relaxation of Vascular Smooth Muscle by 17{beta}-Estradiol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(4): 227 - 234. [Abstract] [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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R. J. McCredie, J. A. McCrohon, L. Turner, K. A. Griffiths, D. J. Handelsman, and D. S. Celermajer Vascular reactivity is impaired in genetic females taking high-dose androgens J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1331 - 1335. [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. Christ and M. Wehling Cardiovascular steroid actions: swift swallows or sluggish snails? Cardiovasc Res, October 1, 1998; 40(1): 34 - 44. [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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S. T. Davidge and Y. Zhang Estrogen Replacement Suppresses a Prostaglandin H Synthase–Dependent Vasoconstrictor in Rat Mesenteric Arteries Circ. Res., August 24, 1998; 83(4): 388 - 395. [Abstract] [Full Text] [PDF]
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E. M. Brooks-Asplund and W. L. Kenney Chronic hormone replacement therapy does not alter resting or maximal skin blood flow J Appl Physiol, August 1, 1998; 85(2): 505 - 510. [Abstract] [Full Text] [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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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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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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K. E. Sorensen, I. Dorup, A. P. Hermann, and L. Mosekilde Combined Hormone Replacement Therapy Does Not Protect Women Against the Age-Related Decline in Endothelium-Dependent Vasomotor Function Circulation, April 7, 1998; 97(13): 1234 - 1238. [Abstract] [Full Text] [PDF]
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