(Circulation. 1995;91:2619-2626.)
© 1995 American Heart Association, Inc.
Articles |
17ß-Estradiol Inhibits Ca2+ Influx and Ca2+ Release Induced by Thromboxane A2 in Porcine Coronary Artery
Presented in part at the 15th Scientific Meeting of the International Society of Hypertension, Melbourne, Australia, March 22, 1994.
From the Department of Geriatrics, Faculty of Medicine, and Department of Veterinary Pharmacology, Faculty of Agriculture (H.K.), University of Tokyo, Japan.
Correspondence to Shu-Zhong Han, MD, PhD, Department of Geriatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan.
Background We wished to investigate the possible mechanism of the protective effect of estrogen replacement on coronary atherosclerosis observed in postmenopausal women.
Methods and Results Cytosolic Ca2+ concentration ([Ca2+]i) and contraction were measured simultaneously in fura 2–loaded porcine coronary arterial strips stimulated by the thromboxane A2 analogue U46619 and high-K+ depolarization in the presence and absence of 17ß-estradiol. Pretreatment with 17ß-estradiol (30 nmol/L to 30 µmol/L) inhibited the sustained elevation of [Ca2+]i and the sustained contraction induced by 300 nmol/L U46619. Higher concentrations of 17ß-estradiol (1 to 100 µmol/L) also inhibited the U46619-induced transient increase in [Ca2+]i and contraction in the absence of extracellular Ca2+. In the strips precontracted by 90 mmol/L K+, 17ß-estradiol (30 µmol/L) inhibited the increases in [Ca2+]i and contraction to resting levels. In contrast, 30 µmol/L 17ß-estradiol only partially inhibited the U46619-induced sustained contraction, despite complete inhibition of the sustained increase in [Ca2+]i. Verapamil (10 µmol/L) also strongly inhibited the sustained increase in [Ca2+]i induced by 300 nmol/L U46619, with a partial inhibition of the U46619-induced sustained contraction. A subsequent addition of 30 µmol/L 17ß-estradiol did not show an additional inhibitory effect on either the [Ca2+]i or the tension after the addition of verapamil. 17ß-Estradiol (10 µmol/L) also inhibited the increase in [Ca2+]i and the contraction induced by cumulative addition of Ca2+ in the strips pretreated with 90 mmol/L K+. However, 17ß-estradiol did not change the slope of the [Ca2+]i-tension curves. 17ß-Estradiol (10 µmol/L) had no effect on the levels of cAMP and cGMP in the coronary strips.
Conclusions 17ß-Estradiol inhibits the contraction of coronary vascular smooth muscle mainly by inhibiting Ca2+ influx without changing Ca2+ sensitivity of contractile elements. The Ca2+ channel blocker–like action of 17ß-estradiol may explain at least a part of the antiatherosclerotic effect of estrogen.
Key Words: hormones • calcium • thromboxane • arteries
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 M. Koga, K. Hirano, J. Nishimura, H. Nakano, and H. Kanaide Endothelium-Dependent and Independent Enhancement of Vascular Contractility in the Ovariectomized Rabbit Reproductive Sciences, July 1, 2004; 11(5): 272 - 279. [Abstract] [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 R. E White, G. Han, M. Maunz, C. Dimitropoulou, A. M El-Mowafy, R. S Barlow, J. D Catravas, C. Snead, G. O Carrier, S. Zhu, et al. Endothelium-independent effect of estrogen on Ca2+-activated K+ channels in human coronary artery smooth muscle cells Cardiovasc Res, February 15, 2002; 53(3): 650 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A Babiker, L. J De Windt, M. van Eickels, C. Grohe, R. Meyer, and P. A Doevendans Estrogenic hormone action in the heart: regulatory network and function Cardiovasc Res, February 15, 2002; 53(3): 709 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M Vila, J. B Martinez-Leon, P. Medina, G. Segarra, R. M Ballester, E. Otero, and S. Lluch U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade Cardiovasc Res, December 1, 2001; 52(3): 462 - 467. [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]
|
|
|
|
|
|
C. R. Rosenfeld, R. E. White, T. Roy, and B. E. Cox Calcium-activated potassium channels and nitric oxide coregulate estrogen-induced vasodilation Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H319 - H328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Wight, C. F. Kung, P. Moreau, H. Takase, N. A. Bersinger, and T. F. Luscher Aging, Serum Estradiol Levels, and Pregnancy Differentially Affect Vascular Reactivity of the Rat Uterine Artery Reproductive Sciences, March 1, 2000; 7(2): 106 - 113. [Abstract] [PDF]
|
|
|
|
 |
|
 T. A. Parker, D. Dunbar Ivy, H. L. Galan, T. R. Grover, J. P. Kinsella, and S. H. Abman Estradiol improves pulmonary hemodynamics and vascular remodeling in perinatal pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, February 1, 2000; 278(2): L374 - L381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Honda, T. Unemoto, and H. Kogo Different Mechanisms for Testosterone-Induced Relaxation of Aorta Between Normotensive and Spontaneously Hypertensive Rats Hypertension, December 1, 1999; 34(6): 1232 - 1236. [Abstract] [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. G. Geary, D. N. Krause, and S. P. Duckles Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H292 - H300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 A. D. Freay, S. W. Curtis, K. S. Korach, and G. M. Rubanyi Mechanism of Vascular Smooth Muscle Relaxation by Estrogen in Depolarized Rat and Mouse Aorta : Role of Nuclear Estrogen Receptor and Ca2+ Uptake Circ. Res., August 19, 1997; 81(2): 242 - 248. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Karaki, H. Ozaki, M. Hori, M. Mitsui-Saito, K.-I. Amano, K.-I. Harada, S. Miyamoto, H. Nakazawa, K.-J. Won, and K. Sato Calcium Movements, Distribution, and Functions in Smooth Muscle Pharmacol. Rev., June 1, 1997; 49(2): 157 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lou, T. Kodama, Y. J. Zhao, P. Maurice, Y. N. Wang, N. Katz, and M. L. Foegh Inhibition of Transplant Coronary Arteriosclerosis in Rabbits by Chronic Estradiol Treatment Is Associated With Abolition of MHC Class II Antigen Expression Circulation, December 15, 1996; 94(12): 3355 - 3361. [Abstract] [Full Text]
|
|
|
|
|
|
V. Guetta and R. O. Cannon III Cardiovascular Effects of Estrogen and Lipid-Lowering Therapies in Postmenopausal Women Circulation, May 15, 1996; 93(10): 1928 - 1937. [Full Text]
|
|
|
|
|
|
L. A. Lipsitz, C. M. Connelly, M. Kelley-Gagnon, D. K. Kiely, and R. J. Morin Effects of Chronic Estrogen Replacement Therapy on Beat-to-Beat Blood Pressure Dynamics in Healthy Postmenopausal Women Hypertension, October 1, 1995; 26(4): 711 - 715. [Abstract] [Full Text]
|
|