EFEK 17β-ESTRADIOL TERHADAP DENSITAS RESEPTOR ADRENERGIK-αIDDAN KONTRAKTILITAS OTOT POLOS PEMBULUH DARAH TIKUS

Authors

  • Nurdiana Nurdiana Laboratorium Farmakologi Fakultas Kedokteran Universitas Brawijaya Malang

DOI:

https://doi.org/10.21776/ub.jkb.2008.024.02.6

Abstract

The incidence of hypertension in menopausal and post menopausal women related to plasma estrogen leveland sympathetic nervous activity. Estrogen may have a specific effect to modulate adrenergic vasoconstriction by modulating adrenergic receptors. Blood vessels contractility is regulated mainly by the sympathetic nervous system, in aorta mediated particularly by  α1Dadrenergic receptor.We hypothesize that 17βestradiol decreases vascular smooth muscle contractility by decreasing  α1Dadrenergic receptor density. To prove the above mechanism in the present study we performed several interrelated assays, i.e bioassay using isolated organ and protein blotting. An isolated rat aortic ring without endothelium (2-3 month,150-200 gram) was incubated in 17β-estradiol (10-5M, 10-4M,and 10-3M ) for two hours prior to stimulation using phenylephrine as α1Dadrenergic receptor agonist. The response of the rat aortic ring to the stimulation of α1Dadrenergic receptor agonist was measured as the subsequent change on aortic contractility using bioassay, and the change of  α1Dadrenergic receptor density using Western and dotblot.

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References

Guyton A.C. Textbook of Medical Physiology. Eight Edition. United State of America: WB Saunders Company;1991;87-94.

Martini. Fundamentale of anatomy & physiology. sixth edition. San Franscisco: Pearson Education,Inc,2004;722-735.

Stampfer MJ,Golditz GA,Willett WC. Postmenopausal Estrogen Therapy and cardiovascular disease.N Eng J Med,1991;325:756-762.

Belchetz, P.E. Hormonal Treatment of Postmenopausal women. N.Engl J. Med,1994;330:1062-1071.

Barret-Connor E, Bush T.Estrogen And Coronary Heart Desease in Women. JAMA,1991;265:1861-1867.

Wenger N.K., Speroff L., Packard B. Cardiovascular Health And Disease in Women. New England, Journal of Medicine,1993;329: 247-256.

Ho and Liao. Non-nuclear Actions of Estrogen: New Targets for Prevention and Treatment of Cardiovascular Disease, Molecular Intervention,2002; 2:219-228.

Lutuola H. Blood Pressure and Hemodynamic in Postmenopausal Woman During Estradiol-17 β Substitution. Annals of Clinical Research, 1983, Suppl.38);15:1-121.

Cagnacci A, Rovati L, Zanni A, Malmusi S, Facchinetti F, and Volpe A. Physiological doses of estradiol decrease nocturnal blood pressure in normotensive postmenopausal women. Am J Physiol Heart Circ Physiol,1999; 276: H1355-H1360.

Pines AThe Effects of Hormon Replacement therapy in NormalPostmeno pausal Women: Measurement of Doppler-Derived Parameters of Aortic Flow. American Journal of Obstetrics and Ginecology,1991;164: 806-812.

Ginsburg J., Hardiman P. Cardiovascular Effects of Transdermal Oestradiol inPostmenopausal Women. Annals of the New York Academy of Sciences,1990;592:424-425

Volterrani M, Rosano, G. M. C., Collins P. *Effect of Estradiol -17βUpon Forearm Blood Flow on Menopausal Women : A Double Blind Randomized Study, Circulation,1993;88;4 (Suppl.2):1-376.

Magnes

Zhang Y, Davidge S.T. Effect of estrogen replacement on vasocons trictor responses in rat mesenteric arteries. Hypertension,1999; 34:1117-1122.

Freay AD, Curtis SW,Korach KS, Rubanyi GM. Mechanism of vascular smooth muscle relaxation by estrogen in depolarized rat and mouse aorta role ofnuclear estrogen receptor and Ca++ uptake. Circulation Research,1997;81:242-248.

Andersen H.L., Weis J.U., Fjalland B., Korsgaard N. Effect of Acute And Long-term Treatment With 17-β- Estradiol on The Vasomotor Responses in The Rat Aorta, British Journal of Pharmacology,1999;126: 159-168.

Gruber CJ,Tschugguel W, Schneeberger C, Huber JC. Production and Action of Estrogens. The New England Journal of Medicine, 2002; 346:340-352.

Mendelsohn M.E., Karas R.H.The Protective Effect of Estrogen on the Cardiovascular System. N Engl J Med,1999; 340(23):1801.

Hoffman B.B.,and Taylor P. Neurotrasmission, The Autonomic and Somatic Motor Nervous System in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, Editors Hardman J.G., Limbird L.E.,Consulting Editor Goodman Gilman A, Tenth Edition,USA, The McGraw-Hill Companies, 2001:115-155.

Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. USA,Proc Natl Acad Sci,1994;91:5212-5216.

Binko J, Majewski H. 17ß-Estradiol reduces vasoconstriction in endothelium-denuded rat aortas through inducible NOS. Am J Physiol , 1998;274:H853-H859.

Geraldes P, Sirois MG, Bernatchez PN,Tanguay JF. Estrogen regulation of endothelial and smooth muscle cell migration and proliferation: role of p38 and p42/44 mitogen-activated protein kinase. 2002; Arterioscler Thromb Vasc Biol 22: 1585-1590.

Dubey RK, Gillespie DG., Imthurn B., Rosselli M., Jackson EK and Keller PJ. Phytoestrogens inhibit growth and MAP kinase activity in human aortic smooth muscle cells. Hypertension, 1999;33:177-182

Bacakova L, Kunes J.Gender differences in growth of vascular smooth muscle cells isolated from hypertensive and normotensive rats.Clin Exp Hypertens, 20O0;22:33-44. (abstract)

Thomas G., Ito K, Zikic E., Bhatti T., Han C and Ramwell PW. Specific Inhibition of The Contraction of The Aorta by Estradiol 17 β.J Pharm Exp Therapy, 1995;273:1544-1550.

Gosh MN.Fundamentals of Experimental Pharmacology.Calcuta, Scientific Book Agency, 1971;27-69.

Perry WLM. Pharmacological Experiments on Isolated Preparation, 2 nd Ed, Edinburg: E & S Livingstone, 1970:58-87.

Bowman W.C, Rand M.J.Textbook of Pharmacology, 2 nd ed, Blackwell Scientific Publication, Melbourn; 1984.

Piascik M.T., Hrometz S.L., Edelmann S.E., Guarino R.D.m Hadley R.W. and Brown R.D. Immunocytochemical Localization of The α1b

Adrenergic receptor and The Contribution of This and The Other Subtype to Vascular Smooth Muscle Contraction Analysys With Selective Ligands and

Antisense Oligonucleotides. J Pharmacol Exp Ther,1997;283: 854-868.

Hrometz, S.L., Edelmann, S.E., McCune, D.F., etal. Expression of Multiple alpha 1-adrenergic receptorson Vascular Smooth Muscle Correlation With the Regulation of Contraction. J.Pharmacol. Exp. Ther, 1999; 290:452-463.

Ross,E.M.Pharmacodynamics: Mechanism of Drug Actions and TheRelationship Between Drug Concentration And Effectin Goodman & Gilman’s The Pharmacological Basis of Therapeutics, Eight edition, Vol.1, Editor Goodman Gilman,A, Rall T.W., Nies AS, Taylor P., New York: Pergamon Press,

; p33-48.

Wynne F.L., Payne J.A., Cain A.E., Reckelhoff J.F., Khalil R.A. Age Related Reduction in Estrogen Receptor- mediated Mechanisms of Vascular Relaxation in Female Spontaneously Hypertensive Rats, Hypertension. 2004;43:405.

Insel P.A. Adrenergic Receptor- Evolving Concepts and ClinicalImplications. The New England Journal of Medicine,1996;334: 580-585.

Piascik MT, Perez DM. α1-adrenergic receptor:New insight and directions. J Pharm. Exp. Ther., 2001; 298:403-410.

Bourne HR, Von Zastrow M. Drug Receptor & PharmacodynamicsinBasic & Clinical Pharmacology, Eight edition, Editor: Katzung BG, International Edition,Lange Medical books/McGraw-Hill,London, 2001; 9-34.

Rudner X.L., Berkowitz D.E., Booth J.V., et al.Subtype Specific Regulation of Human Vascular Alpha (1)-Adrenergic Receptor by Vessel Beds and Age, Circulation, 1999;100:2336-2343.

Guarino RD, Perez DM and Piascik MT. α1-Adrenergic receptor Subtypes. Cell Signal, 1996 8:323-333.

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Published

2013-03-11

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Research Article