Circulation, Vol 90, 786-791, Copyright © 1994 by American Heart Association
DM Gilligan, DM Badar, JA Panza, AA Quyyumi and RO Cannon 3rd
BACKGROUND: Although hormone replacement therapy has been associated with
reduction of cardiovascular events in postmenopausal women, the mechanisms
that mediate this apparent benefit are unclear. Because improvement in
vasomotor function may represent one of the beneficial effects of estrogen
administration, we investigated the acute effects of physiological levels
of estrogen on the vascular responses of estrogen-deficient postmenopausal
women. METHODS AND RESULTS: The study included 40 postmenopausal women 60
+/- 8 years old (mean +/- SD), 20 of whom had one or more conditions
associated with vascular dysfunction (hypertension, hypercholesterolemia,
diabetes, or coronary artery disease). The forearm vascular responses to
the endothelium-dependent vasodilator acetylcholine were studied before and
during infusion of 17 beta-estradiol into the ipsilateral brachial artery.
In 31 subjects, the effect of estradiol on the responses to the
endothelium-independent vasodilator sodium nitroprusside was also studied.
Women with risk factors for vascular dysfunction had significantly reduced
vasodilator responses to acetylcholine (P = .01) and to sodium
nitroprusside (P < .001) compared with healthy subjects. Intra-arterial
infusion of 17 beta-estradiol increased the forearm venous estradiol
concentration from 16 +/- 10 to 318 +/- 188 pg/mL, levels typical of
reproductive-age women at midcycle, but caused no vasodilation. However,
estradiol potentiated the forearm vasodilation induced by acetylcholine by
18 +/- 30% (P < .001) in women with risk factors for vascular
dysfunction and by 14 +/- 23% (P = .03) in healthy women. Estradiol also
potentiated the forearm vasodilation induced by sodium nitroprusside in
women with risk factors for vascular dysfunction by 14 +/- 21% (P <
.001) but not in healthy women. CONCLUSIONS: Physiological levels of 17
beta- estradiol selectively potentiate endothelium-dependent vasodilation
in healthy postmenopausal women and potentiate both endothelium-dependent
and endothelium-independent vasodilation in post-menopausal women with risk
factors for atherosclerosis and evidence of impaired vascular function.
These vascular effects may be partly responsible for the long- term benefit
of estrogen therapy on cardiovascular events in postmenopausal women.
ARTICLES
Acute vascular effects of estrogen in postmenopausal women
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
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M. Giacche, A. Vuagnat, S. C. Hunt, P. N. Hopkins, N. D. L. Fisher, M. Azizi, P. Corvol, G. H. Williams, and X. Jeunemaitre Aldosterone Stimulation by Angiotensin II : Influence of Gender, Plasma Renin, and Familial Resemblance Hypertension, March 1, 2000; 35(3): 710 - 716. [Abstract] [Full Text] [PDF]
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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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M. Elsheikh, R. Bird, B. Casadei, G. S. Conway, and J. A. H. Wass The Effect of Hormone Replacement Therapy on Cardiovascular Hemodynamics in Women with Turner's Syndrome J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 614 - 618. [Abstract] [Full Text]
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G. W. de Valk-de Roo, C. D.A. Stehouwer, P. Meijer, V. Mijatovic, C. Kluft, P. Kenemans, F. Cohen, S. Watts, and C. Netelenbos Both Raloxifene and Estrogen Reduce Major Cardiovascular Risk Factors in Healthy Postmenopausal Women : A 2-Year, Placebo-Controlled Study Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2993 - 3000. [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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N. Charkoudian, D. P. Stephens, K. C. Pirkle, W. A. Kosiba, and J. M. Johnson Influence of female reproductive hormones on local thermal control of skin blood flow J Appl Physiol, November 1, 1999; 87(5): 1719 - 1723. [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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 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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 M. A. Valverde, P. Rojas, J. Amigo, D. Cosmelli, P. Orio, M. I. Bahamonde, G. E. Mann, C. Vergara, and R. Latorre Acute Activation of Maxi-K Channels (hSlo) by Estradiol Binding to the Subunit Science, September 17, 1999; 285(5435): 1929 - 1931. [Abstract] [Full Text]
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C. Giannattasio, M. Failla, A. Grappiolo, M. L. Stella, A. Del Bo, M. Colombo, and G. Mancia Fluctuations of Radial Artery Distensibility Throughout the Menstrual Cycle Arterioscler Thromb Vasc Biol, August 1, 1999; 19(8): 1925 - 1929. [Abstract] [Full Text] [PDF]
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U. Brehme, B. Bruck, N. Gugel, M. Wehrmann, S. Hanke, G. Finking, F. W. Schmahl, and H. Hanke Aortic Plaque Size and Endometrial Response in Cholesterol-Fed Rabbits Treated With Estrogen Plus Continuous or Sequential Progestin Arterioscler Thromb Vasc Biol, August 1, 1999; 19(8): 1930 - 1937. [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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L A Fitzpatrick, M Ruan, J Anderson, T Moraghan, and V Miller Gender-related differences in vascular smooth muscle cell proliferation: implications for prevention of arteriosclerosis Lupus, June 1, 1999; 8(5): 397 - 401. [Abstract] [PDF]
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G. Gardner, C. L. Banka, K. A. Roberts, A. E. Mullick, and J. C. Rutledge Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17ß-Estradiol Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 854 - 861. [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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M. Christ, A. Gunther, M. Heck, B. M. W. Schmidt, E. Falkenstein, and M. Wehling Aldosterone, Not Estradiol, Is the Physiological Agonist for Rapid Increases in cAMP in Vascular Smooth Muscle Cells Circulation, March 23, 1999; 99(11): 1485 - 1491. [Abstract] [Full Text] [PDF]
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I. C. D. Westendorp, M. L. Bots, D. E. Grobbee, R. S. Reneman, A. P. G. Hoeks, N. M. Van Popele, A. Hofman, and J. C. M. Witteman Menopausal Status and Distensibility of the Common Carotid Artery Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 713 - 717. [Abstract] [Full Text] [PDF]
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Y. S. Prakash, A. A. Togaibayeva, M. S. Kannan, V. M. Miller, L. A. Fitzpatrick, and G. C. Sieck Estrogen increases Ca2+ efflux from female porcine coronary arterial smooth muscle Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H926 - H934. [Abstract] [Full Text] [PDF]
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 R. D. Minshall, K. Miyagawa, C. C. Chadwick, M. J. Novy, and K. Hermsmeyer In vitro modulation of primate coronary vascular muscle cell reactivity by ovarian steroid hormones FASEB J, October 1, 1998; 12(13): 1419 - 1429. [Abstract] [Full Text]
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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. 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. Kim-Schulze, W. L. Lowe Jr, and H. W. Schnaper Estrogen Stimulates Delayed Mitogen-Activated Protein Kinase Activity in Human Endothelial Cells via an Autocrine Loop That Involves Basic Fibroblast Growth Factor Circulation, August 4, 1998; 98(5): 413 - 421. [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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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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D. O. Ruehlmann, J. R. Steinert, M. A. Valverde, R. Jacob, and G. E. Mann Environmental estrogenic pollutants induce acute vascular relaxation by inhibiting L-type Ca2+ channels in smooth muscle cells FASEB J, May 1, 1998; 12(7): 613 - 619. [Abstract] [Full Text]
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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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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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