Abstract
It is now well known that 17β-estradiol has an endothelium-independent, non-genomic vasorelaxant effect. We hypothesized that 17β-estradiol has its non-genomic effect on calcium-independent contraction in de-endothelialized rat aortic rings. Rat aortic ring preparations were mounted in organ baths and exposed to contractile agents. 17β-Estradiol (8, 20 or 50 μM), but not 17α-estradiol, concentration-dependently decreased the tension induced by 1.0 μM phenylephrine (PE) in the presence, but not in the absence, of calcium in the solution. Pretreatment with 17β-estradiol concentration-dependently inhibited vascular contractions induced by cumulative addition of PE or calcium and almost completely abolished those induced by cumulative addition of Bay K8644, a calcium channel opener. Furthermore, 17β-estradiol also concentration-dependently decreased the tension induced by 0.3 μM phorbol 12,13-dibutyrate (PDBu), a protein kinase C activator, in the presence of calcium in the solution, but not in the absence of calcium in the solution. Pretreatment with 17β-estradiol had little effect on vascular contractions induced by PDBu or PE or on PE-induced mitogen-activated protein kinase (MAPK) activation in calcium-free Krebs solution. These results suggest that 17β-estradiol inhibits calcium-dependent, but not calcium-independent, vascular contraction.
Similar content being viewed by others
References
Andersen HL, Weis JU, Fjalland B, Korsgaard N (1999) Effect of acute and long-term treatment with 17β-estradiol on the vasomotor responses in the rat aorta. Br J Pharmacol 126:159–168
Browne M, Connolly C, Docherty JR (1999) Vascular actions of 17β-oestradiol in rat aorta and mesenteric artery. J Auton Pharmacol 19:291–299
Dessy C, Kim I, Sougnez CL, Laporte R, Morgan KG (1998) A role for MAP kinase in differentiated smooth muscle contraction evoked by α-adrenoceptor stimulation. Am J Physiol 275:C1081–C1086
Fukata Y, Amano M, Kaibuchi K (2001) Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol Sci 22:32–39
Hai CM, Murphy RA (1989) Ca2+, crossbridge phosphorylation, and contraction. Annu Rev Physiol 51:285–298
Han SZ, Karaki H, Ouchi Y, Akishita M, Orimo H (1995) 17β-Estradiol inhibits Ca2+ influx and Ca2+ release induced by thromboxane A2 in porcine coronary artery. Circulation 91:2619–2626
Horowitz A, Menice CB, Laporte R, Morgan KG (1996) Mechanisms of smooth muscle contractions. Physiol Rev 76:976–1003
Jiang C, Sarrel PM, Lindsay DC, Poole-Wilson PA, Collins P (1991) Endothelium-dependent relaxation of rabbit coronary artery by 17β-oestradiol in vivo. Br J Pharmacol 104:1033–1037
Katsuyama H, Morgan KG (1993) Mechanisms of Ca2+-independent contraction in single permeabilized ferret aorta cells. Circ Res 72:651–657
Khalil RA, Morgan KG (1993) PKC-mediated redistribution of mitogen-activated protein kinase during smooth muscle cell activation. Am J Physiol 265:C406–C411
Kim YH, Kim JH, Kim MK, Baek WY Kim IK (1999) Effect of heat shock on the vascular contractility in isolated rat aorta. J Pharmacol Toxicol Methods 42:171–174
Kim IK, Park TG, Kim YH, Cho JW, Kang B, Kim CY (2004) Heat-shock response is associated with enhanced contractility of vascular smooth muscle in isolated rat aorta. Naunyn-Schmiedeberg’s Arch Pharmacol 369:402–407
Kitazawa T, Hamada E, Kuazawa K, Gaznabi AKM (1997) Non-genomic mechanism of 17β-oestradiol-induced inhibition of contraction in mammalian vascular smooth muscle. J Physiol (Lond) 499:497–511
Levin ER (2001) Cell localization, physiology, and nongenomic actions of estrogen receptors. J Appl Physiol 91:1860–1867
Liou YM, Morgan KG (1994) Redistribution of protein kinase C isoforms in association with vascular hypertrophy of rat aorta. Am J Physiol 267:C980–C989
Montgomery S, Shaw L, Pantelides N, Taggart M, Austin C (2003) Acute effects of oestrogen receptor subtype-specific agonists on vascular contractility. Br J Pharmacol 139:1249–1253
Morgan KG, Leinweber BD (1998) PKC-dependent signalling mechanisms in differentiated smooth muscle. Acta Physiol Scand 164:495–505
Mugge A, Riedel M, Barton M, Kuhn M, Lichtlen PR (1993) Endothelium independent relaxation of human coronary arteries by 17β-oestradiol in vitro. Cardiovasc Res 27:1939–1942
National Institutes of Health (1996) Guide for the care and use of laboratory animals. NIH publication no. 85-23, revised edn. NIH, Bethesda, MD
Pappas TC, Gametchu B, Watson CS (1995) Membrane estrogen receptors identified by multiple antibody labeling and impeded-ligand binding. FASEB J 9:404–410
Park YH, Park HK, Lee HJ, Park SM, Choi SW, Lee WJ (2002) Phytoestrogen-induced phosphorylation of MAP kinase in osteoblast is mediated by membrane estrogen receptor. Korean J Physiol Pharmacol 6:165–169
Salom JB, Burguete MC, Perez-Asensio FJ, Centeno JM, Torregrosa G, Iborch E (2002) Acute relaxant effects of 17β-estradiol through non-genomic mechanisms in rabbit carotid artery. Steroids 67:339–346
Schramm M, Thomas G, Towart R, Franckowiak G (1983) Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature 303:535–537
Shaw L, Taggart MJ, Austin C (2000) Mechanisms of 17β-oestradiol induced vasodilatation in isolated pressurized rat small arteries. Br J Pharmacol 129:555–565
Singer HA, Oren JW, Benscoter HA (1989) Myosin light chain phosphorylation in 32P-labeled rabbit aorta stimulated by phorbol 12,13-dibutyrate and phenylephrine. J Biol Chem 264:21215–21222
Somlyo AP, Somlyo AV (1994) Signal transduction and regulation in smooth muscle. Nature 372:231–236
Acknowledgements
The authors are extremely grateful to Dr. Michael Taggart (University of Manchester, Manchester, UK) for his critical reading of this manuscript. This work was supported by a grant no. R04-2001-00086 from the Korea Science and Engineering Foundation (to W.-J. Lee).
Author information
Authors and Affiliations
Corresponding author
Additional information
H.-A. Lee and Y. Seong contributed equally to this work.
Rights and permissions
About this article
Cite this article
Lee, HA., Seong, Y., Lee, WJ. et al. 17β-Estradiol inhibits calcium-dependent, but not calcium-independent, contraction in isolated rat aorta. Naunyn-Schmiedeberg's Arch Pharmacol 371, 152–157 (2005). https://doi.org/10.1007/s00210-004-1017-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-004-1017-3