Mechanisms of estrogen-induced vasodilation: in vivo studies in canine coronary conductance and resistance arteries

Cardiovascular Research Institute, University of California at San Francisco, USA.

OBJECTIVES. We sought to examine the immediate vasodilator effect of intracoronary estrogen on epicardial and resistance coronary arteries in 19 dogs. BACKGROUND. Although estrogen reportedly dilates coronary arteries in vitro, the site and mechanisms of its action have not been fully defined in vivo. METHODS. Epicardial coronary artery dimensions and coronary flow velocity were assessed using simultaneous intracoronary two-dimensional and Doppler ultrasound. RESULTS. Estrogen (0.1 and 1 mumol/liter) induced a significant increase in coronary cross-sectional area, flow velocity and volumetric blood flow. Estrogen-induced vasodilation was not influenced either by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME) (100 mumol/liter intracoronary), indomethacin (5 mg/kg body weight intravenously), propranolol (0.75 mg/kg intravenously) or the classic estrogen receptor antagonist ICI 182,780 (10 mumol/liter). Balloon denudation of the endothelium did not attenuate estrogen-induced epicardial vasodilation. Pretreatment with glibenclamide (10 mumol/liter) attenuated estrogen-induced vasodilation only in epicardial arteries, as did verapamil (0.1 mumol/liter). Estrogen had no effect on a phenylephrine dose-response curve in either epicardial coronary arteries or the microcirculation. CONCLUSIONS. Acute estrogen-induced dilation in canine coronary arteries is endothelium independent and is not mediated by the classic intracellular estrogen receptor but through non-genomic mechanisms, presumably at the membrane level, which in epicardial arteries may include effects on adenosine triphosphate-sensitive potassium or calcium channels, or both.

This article has been cited by other articles:

				P.-A. Scott, A. Tremblay, M. Brochu, and J. St-Louis Vasorelaxant action of 17 -estradiol in rat uterine arteries: role of nitric oxide synthases and estrogen receptors Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3713 - H3719. [Abstract] [Full Text] [PDF]

				B. A. Parker, S. L. Smithmyer, J. A. Pelberg, A. D. Mishkin, M. D. Herr, and D. N. Proctor Sex differences in leg vasodilation during graded knee extensor exercise in young adults J Appl Physiol, November 1, 2007; 103(5): 1583 - 1591. [Abstract] [Full Text] [PDF]

				T. Traupe, C. D. Stettler, H. Li, E. Haas, I. Bhattacharya, R. Minotti, and M. Barton Distinct Roles of Estrogen Receptors {alpha} and {beta} Mediating Acute Vasodilation of Epicardial Coronary Arteries Hypertension, June 1, 2007; 49(6): 1364 - 1370. [Abstract] [Full Text] [PDF]

				R. R. Magness, T. M. Phernetton, T. C. Gibson, and D.-b. Chen Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17{beta}-treated, intact follicular and pregnant sheep J. Physiol., May 15, 2005; 565(1): 71 - 83. [Abstract] [Full Text] [PDF]

				N. Kipshidze, G. Dangas, M. Tsapenko, J. Moses, M. B. Leon, M. Kutryk, and P. Serruys Role of the endothelium in modulating neointimal formation: Vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions J. Am. Coll. Cardiol., August 18, 2004; 44(4): 733 - 739. [Abstract] [Full Text] [PDF]

				L. W. Lissin, R. Oka, S. Lakshmi, and J. P Cooke Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia Vascular Medicine, February 1, 2004; 9(1): 26 - 30. [Abstract] [PDF]

				M. Nishino, H.-J. Youn, D. Gheorghevici, C. Zellner, T. M. Chou, K. Sudhir, and R. F. Redberg Effect of Intracoronary Estradiol on Postischemic Microvascular Damage in a Porcine Model: A Myocardial Contrast Echocardiographic Study Angiology, November 1, 2003; 54(6): 701 - 709. [Abstract] [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]

				C.-H. Tsai, S.-F. Su, T.-F. Chou, and T.-M. Lee Differential Effects of Sarcolemmal and Mitochondrial KATP Channels Activated by 17beta -Estradiol on Reperfusion Arrhythmias and Infarct Sizes in Canine Hearts J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 234 - 240. [Abstract] [Full Text] [PDF]

				J. R. Rouleau, A. Dagnault, D. Simard, B. Lavallee, A. Belanger, A. Blouin, and J. G. Kingma Jr. Effect of estrogen replacement therapy on distribution of myocardial blood flow in female anesthetized rabbits Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1407 - H1412. [Abstract] [Full Text] [PDF]

				R. Kakucs, S. Varbiro, G. L. Nadasy, E. Monos, and B. Szekacs Acute, Nongenomic Vasodilatory Action of Estradiol Is Attenuated by Chronic Estradiol Treatment Experimental Biology and Medicine, June 1, 2001; 226(6): 538 - 542. [Abstract] [Full Text] [PDF]

				G. A. Figtree, C. M. Webb, and P. Collins Tamoxifen Acutely Relaxes Coronary Arteries by an Endothelium-, Nitric Oxide-, and Estrogen Receptor-Dependent Mechanism J. Pharmacol. Exp. Ther., November 1, 2000; 295(2): 519 - 523. [Abstract] [Full Text]

				S. E. Reis, R. Holubkov, J. B. Young, B. G. White, J. N. Cohn, and A. M. Feldman Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies J. Am. Coll. Cardiol., August 1, 2000; 36(2): 529 - 533. [Abstract] [Full Text] [PDF]

				G. A. Figtree, H. Griffiths, Y.-Q. Lu, C. M. Webb, K. MacLeod, and P. Collins Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1977 - 1985. [Abstract] [Full Text] [PDF]

				A. A. Nekooeian and C. C. Y. Pang Effects of estrogen on venous function in rats with chronic heart failure Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1941 - H1947. [Abstract] [Full Text] [PDF]

				L. R. Peterson, M. Courtois, L. F. Peterson, M. R. Peterson, V. G. Dávila-Román, R. J. Spina, and B. Barzilai Estrogen Increases Hyperemic Microvascular Blood Flow Velocity in Postmenopausal Women J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2000; 55(3): 174M - 179. [Abstract] [Full Text]

				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]

				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]

				G. A. Figtree, Y.-q. Lu, C. M. Webb, and P. Collins Raloxifene Acutely Relaxes Rabbit Coronary Arteries In Vitro by an Estrogen Receptor–Dependent and Nitric Oxide–Dependent Mechanism Circulation, September 7, 1999; 100(10): 1095 - 1101. [Abstract] [Full Text] [PDF]

				V M Miller Gender and vascular reactivity Lupus, June 1, 1999; 8(5): 409 - 415. [Abstract] [PDF]

				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]

				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]

				C. Zellner, A. A. Protter, E. Ko, M. R. Pothireddy, T. DeMarco, S. J. Hutchison, T. M. Chou, K. Chatterjee, and K. Sudhir Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance and resistance arteries Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H1049 - H1057. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				K. Sudhir, M. D. Esler, G. L. Jennings, and P. A. Komesaroff Estrogen Supplementation Decreases Norepinephrine-Induced Vasoconstriction and Total Body Norepinephrine Spillover in Perimenopausal Women Hypertension, December 1, 1997; 30(6): 1538 - 1543. [Abstract] [Full Text]

				K. Sudhir, E. Ko, C. Zellner, H. E. Wong, S. J. Hutchison, T. M. Chou, and K. Chatterjee Physiological Concentrations of Estradiol Attenuate Endothelin 1–Induced Coronary Vasoconstriction In Vivo Circulation, November 18, 1997; 96(10): 3626 - 3632. [Abstract] [Full Text]

				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]

				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]

				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]

				K. Node, M. Kitakaze, H. Kosaka, T. Minamino, H. Funaya, and M. Hori Amelioration of Ischemia- and Reperfusion-Induced Myocardial Injury by 17ß-Estradiol : Role of Nitric Oxide and Calcium-Activated Potassium Channels Circulation, September 16, 1997; 96(6): 1953 - 1963. [Abstract] [Full Text]

				N. D. L. Fisher, C. Ferri, C. Bellini, A. Santucci, R. Gleason, G. H. Williams, N. K. Hollenberg, and E. W. Seely Age, Gender, and Non-modulation : A Sexual Dimorphism in Essential Hypertension Hypertension, April 1, 1997; 29(4): 980 - 985. [Abstract] [Full Text]

				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]

				S. L. Hale, Y. Birnbaum, and R. A. Kloner Estradiol, Administered Acutely, Protects Ischemic Myocardium in Both Female and Male Rabbits Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(1): 47 - 52. [Abstract] [PDF]

				T. M. Chou, K. Sudhir, S. J. Hutchison, E. Ko, T. M. Amidon, P. Collins, and K. Chatterjee Testosterone Induces Dilation of Canine Coronary Conductance and Resistance Arteries In Vivo Circulation, November 15, 1996; 94(10): 2614 - 2619. [Abstract] [Full Text]

				K. Sudhir, G. L. Jennings, J. W. Funder, and P. A. Komesaroff Estrogen Enhances Basal Nitric Oxide Release in the Forearm Vasculature in Perimenopausal Women Hypertension, September 1, 1996; 28(3): 330 - 334. [Abstract] [Full Text]