(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
This article has been cited by other articles:
 |
|
 |
|
  L. R. Peterson, P. F. Soto, P. Herrero, B. S. Mohammed, M. S. Avidan, K. B. Schechtman, C. Dence, and R. J. Gropler Impact of Gender on the Myocardial Metabolic Response to Obesity J. Am. Coll. Cardiol. Img., July 1, 2008; 1(4): 424 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Han, J. H. Bae, D. R. Holmes Jr, R. J. Lennon, E. Eeckhout, G. W. Barsness, C. S. Rihal, and A. Lerman Sex differences in atheroma burden and endothelial function in patients with early coronary atherosclerosis Eur. Heart J., June 1, 2008; 29(11): 1359 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goel, D. Thor, L. Anderson, and R. Rahimian Sexual dimorphism in rabbit aortic endothelial function under acute hyperglycemic conditions and gender-specific responses to acute 17{beta}-estradiol Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2411 - H2420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rees, J. Stevenson, and on behalf of the British Menopause Society Council Primary prevention of coronary heart disease in women Menopause Int, March 1, 2008; 14(1): 40 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Collins, M. Flather, B. Lees, R. Mister, A. J. Proudler, J. C. Stevenson, and on behalf of the WHISP (Women's Hormone Interventi Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study Eur. Heart J., September 1, 2006; 27(17): 2046 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J C Kaski Cardiac syndrome X in women: the role of oestrogen deficiency Heart, May 1, 2006; 92(suppl_3): iii5 - iii9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Cruz, G. Douglas, J.-A Gustafsson, L. Poston, and K. Kublickiene Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-{beta} knockout mice Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H823 - H829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Khalil Sex Hormones as Potential Modulators of Vascular Function in Hypertension Hypertension, August 1, 2005; 46(2): 249 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. T. van der Schouw and D. E. Grobbee Menopausal complaints, oestrogens, and heart disease risk: an explanation for discrepant findings on the benefits of post-menopausal hormone therapy Eur. Heart J., July 2, 2005; 26(14): 1358 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Guo, M. Razandi, A. Pedram, G. Kassab, and E. R. Levin Estrogen Induces Vascular Wall Dilation: MEDIATION THROUGH KINASE SIGNALING TO NITRIC OXIDE AND ESTROGEN RECEPTORS {alpha} AND {beta} J. Biol. Chem., May 20, 2005; 280(20): 19704 - 19710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Kaufmann and P. G. Camici Myocardial Blood Flow Measurement by PET: Technical Aspects and Clinical Applications J. Nucl. Med., January 1, 2005; 46(1): 75 - 88. [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Egan, J. A. Lawson, S. Fries, B. Koller, D. J. Rader, E. M. Smyth, and G. A. FitzGerald COX-2-Derived Prostacyclin Confers Atheroprotection on Female Mice Science, December 10, 2004; 306(5703): 1954 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Lu, D. C. Pallas, H. K. Surks, W. E. Baur, M. E. Mendelsohn, and R. H. Karas Striatin assembles a membrane signaling complex necessary for rapid, nongenomic activation of endothelial NO synthase by estrogen receptor {alpha} PNAS, December 7, 2004; 101(49): 17126 - 17131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Head, V. R. Obeyesekere, M. E. Jones, E. R. Simpson, and Z. S. Krozowski Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity Endocrinology, September 1, 2004; 145(9): 4286 - 4291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Waters, D. Gordon, J. E. Rossouw, R. O. Cannon III, P. Collins, D. M. Herrington, J. Hsia, R. Langer, L. Mosca, P. Ouyang, et al. Women's Ischemic Syndrome Evaluation: Current Status and Future Research Directions Report of the National Heart, Lung and Blood Institute Workshop : October 2-4, 2002 : Section 4: Lessons From Hormone Replacement Trials Circulation, February 17, 2004; 109 (6): e53 - e55. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mendelsohn and G. M.C. Rosano Hormonal Regulation of Normal Vascular Tone in Males Circ. Res., December 12, 2003; 93(12): 1142 - 1145. [Full Text] [PDF]
|
|
|
|
|
|
M. Kimura, K. Sudhir, M. Jones, E. Simpson, A.-M. Jefferis, and J. P.F. Chin-Dusting Impaired Acetylcholine-Induced Release of Nitric Oxide in the Aorta of Male Aromatase-Knockout Mice: Regulation of Nitric Oxide Production by Endogenous Sex Hormones in Males Circ. Res., December 12, 2003; 93(12): 1267 - 1271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ferrero, F. Ribichini, G. Matullo, S. Guarrera, S. Carturan, A. Vado, C. Vassanelli, A. Piazza, E. Uslenghi, and W. Wijns Estrogen Receptor-{alpha} Polymorphisms and Angiographic Outcome After Coronary Artery Stenting Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2223 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Lew, P. Komesaroff, M. Williams, T. Dawood, and K. Sudhir Endogenous Estrogens Influence Endothelial Function in Young Men Circ. Res., November 28, 2003; 93(11): 1127 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jokela, P. Dastidar, R. Rontu, A. Salomaki, K. Teisala, T. Lehtimaki, and R. Punnonen Effects of Long-Term Estrogen Replacement Therapy Versus Combined Hormone Replacement Therapy on Nitric Oxide-Dependent Vasomotor Function J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4348 - 4354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Griffiths, M. A. Sader, M. R. Skilton, J. A. Harmer, and D. S. Celermajer Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease J. Am. Coll. Cardiol., August 20, 2003; 42(4): 698 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sanada, Y. Higashi, K. Nakagawa, M. Tsuda, I. Kodama, M. Kimura, K. Chayama, and K. Ohama A Comparison of Low-Dose and Standard-Dose Oral Estrogen on Forearm Endothelial Function in Early Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1303 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-M. Lee, T.-F. Chou, and C.-H. Tsai Differential Role of KATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects Circulation, January 7, 2003; 107(1): 49 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Hickner, G. Kemeny, K. McIver, K. Harrison, and M. E. Hostetler Lower Skeletal Muscle Nutritive Blood Flow in Older Women Is Related to eNOS Protein Content J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2003; 58(1): B20 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Stangl, G. Baumann, and K. Stangl Coronary atherogenic risk factors in women Eur. Heart J., November 2, 2002; 23(22): 1738 - 1752. [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Chambliss and P. W. Shaul Estrogen Modulation of Endothelial Nitric Oxide Synthase Endocr. Rev., October 1, 2002; 23(5): 665 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sanada, Y. Higashi, K. Nakagawa, M. Tsuda, I. Kodama, M. Kimura, K. Chayama, and K. Ohama Hormone Replacement Effects on Endothelial Function Measured in the Forearm Resistance Artery in Normocholesterolemic and Hypercholesterolemic Postmenopausal Women J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4634 - 4641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Iraculis, A. Cequier, J. A. Gomez-Hospital, M. Sabate, J. Mauri, E. Fernandez-Nofrerias, B. Garcia del Blanco, F. Jara, and E. Esplugas Early dysfunction and long-term improvement in endothelium-dependent vasodilation in the infarct-related artery after thrombolysis J. Am. Coll. Cardiol., July 17, 2002; 40(2): 257 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.C. Duncan, J.R. Petrie, M.J. Brosnan, A.M. Devlin, R.A. Bass, D.S. Charnock-Jones, J.M.C. Connell, A.F. Dominiczak, and M.A. Lumsden Is estradiol cardioprotection a nitric oxide-mediated effect? Hum. Reprod., July 1, 2002; 17(7): 1918 - 1924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kenny, K. M. Prestwood, C. A. Gruman, G. Fabregas, B. Biskup, and G. Mansoor Effects of Transdermal Testosterone on Lipids and Vascular Reactivity in Older Men With Low Bioavailable Testosterone Levels J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2002; 57(7): M460 - 465. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. E Rossouw Hormones, genetic factors, and gender differences in cardiovascular disease Cardiovasc Res, February 15, 2002; 53(3): 550 - 557. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Sader and D. S. Celermajer Endothelial function, vascular reactivity and gender differences in the cardiovascular system Cardiovasc Res, February 15, 2002; 53(3): 597 - 604. [Full Text] [PDF]
|
|
|
|
|
|
J. C. Kaski Overview of gender aspects of cardiac syndrome X Cardiovasc Res, February 15, 2002; 53(3): 620 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakano, T. Oshima, R. Ozono, A. Ueda, Y. Oue, H. Matsuura, M. Sanada, K. Ohama, K. Chayama, and M. Kambe Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca2+ influx and raising cyclic adenosine monophosphate Cardiovasc Res, February 15, 2002; 53(3): 634 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fischer, A. Baessler, and H. Schunkert Renin angiotensin system and gender differences in the cardiovascular system Cardiovasc Res, February 15, 2002; 53(3): 672 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Dubey, S. Oparil, B. Imthurn, and E. K. Jackson Sex hormones and hypertension Cardiovasc Res, February 15, 2002; 53(3): 688 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Marra, P. Cotroneo, D. Pitocco, A. Manto, M. A.S. Di Leo, V. Ruotolo, S. Caputo, B. Giardina, G. Ghirlanda, and S. A. Santini Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes: A case for gender difference Diabetes Care, February 1, 2002; 25(2): 370 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Schulman, D. R. Thiemann, P. Ouyang, N. C. Chandra, D. S. Schulman, S. E. Reis, M. Terrin, S. Forman, C. Piva de Albuquerque, R. D. Bahr, et al. Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina J. Am. Coll. Cardiol., January 16, 2002; 39(2): 231 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Sitges, M Heras, E Roig, M Duran, M Masotti, M.J Zurbano, M Roque, and G Sanz Acute and mid-term combined hormone replacement therapy improves endothelial function in post-menopausal women with angina and angiographically normal coronary arteries Eur. Heart J., November 2, 2001; 22(22): 2116 - 2124. [Abstract] [PDF]
|
|
|
|
|
|
M. E. Beyer, G. Yu, H. Hanke, and H. M. Hoffmeister Acute Gender-Specific Hemodynamic and Inotropic Effects of 17{beta}-Estradiol on Rats Hypertension, November 1, 2001; 38(5): 1003 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Komesaroff, M. Fullerton, M. D. Esler, A. Dart, G. Jennings, and K. Sudhir Low-Dose Estrogen Supplementation Improves Vascular Function in Hypogonadal Men Hypertension, November 1, 2001; 38(5): 1011 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Sharma, V. Homuth, and F. C. Luft Hormone replacement therapy and blood pressure in normotensive and hypertensive women Nephrol. Dial. Transplant., May 1, 2001; 16(5): 888 - 890. [Full Text] [PDF]
|
|
|
|
|
|
M. Sanada, Y. Higashi, K. Nakagawa, S. Sasaki, I. Kodama, M. Tsuda, N. Nagai, and K. Ohama Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1529 - 1535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Jhund, N. Dawson, A. P. Davie, N. Sattar, J. Norrie, K. P. J. O'Kane, and J. J. V. McMurray Attenuation of endothelin-1 induced vasoconstriction by 17{beta} estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1367 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chareonthaitawee, P. A Kaufmann, O. Rimoldi, and P. G Camici Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans Cardiovasc Res, April 1, 2001; 50(1): 151 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Paradisi, H. O. Steinberg, A. Hempfling, J. Cronin, G. Hook, M. K. Shepard, and A. D. Baron Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction Circulation, March 13, 2001; 103(10): 1410 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kawano, T. Motoyama, N. Hirai, K. Kugiyama, H. Ogawa, and H. Yasue Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina J. Am. Coll. Cardiol., March 1, 2001; 37(3): 735 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Gonzales, B. R. Walker, and N. L. Kanagy 17{beta}-Estradiol increases nitric oxide-dependent dilation in rat pulmonary arteries and thoracic aorta Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L555 - L564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Higashi, M. Sanada, S. Sasaki, K. Nakagawa, C. Goto, H. Matsuura, K. Ohama, K. Chayama, and T. Oshima Effect of Estrogen Replacement Therapy on Endothelial Function in Peripheral Resistance Arteries in Normotensive and Hypertensive Postmenopausal Women Hypertension, February 1, 2001; 37(2): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Walker, T. S. Dean, T. A. B. Sanders, G. Jackson, J. M. Ritter, and P. J. Chowienczyk The Phytoestrogen Genistein Produces Acute Nitric Oxide-Dependent Dilation of Human Forearm Vasculature With Similar Potency to 17{beta}-Estradiol Circulation, January 16, 2001; 103(2): 258 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Kanashiro and R. A. Khalil Gender-related distinctions in protein kinase C activity in rat vascular smooth muscle Am J Physiol Cell Physiol, January 1, 2001; 280(1): C34 - C45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Mather, E. G. Norman, J. C. Prior, and T. G. Elliott Preserved Forearm Endothelial Responses with Acute Exposure to Progesterone: A Randomized Cross-Over Trial of 17-{beta} Estradiol, Progesterone, and 17-{beta} Estradiol with Progesterone in Healthy Menopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4644 - 4649. [Abstract] [Full Text]
|
|
|
|
|
|
S. Vehkavaara, J. Westerbacka, T. Hakala-Ala-Pietilä, A. Virkamäki, O. Hovatta, and H. Yki-Järvinen Effect of Estrogen Replacement Therapy on Insulin Sensitivity of Glucose Metabolism and Preresistance and Resistance Vessel Function in Healthy Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4663 - 4670. [Abstract] [Full Text]
|
|
|
|
< |