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Estrogen and Endothelial Function

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Women’s Health and Menopause

Abstract

Although observational studies have shown that estrogen can protect women against cardiovascular diseases (CVD), the underlying mechanisms are not fully clarified. Endothelium plays a pivotal role in the control of vascular function and structure; endothelial dysfunction, characterized by reduced or absent nitric oxide (NO) bioavailability linked and/or due to the production of cyclooxygenase-dependent endothelial-derived contracting factors (EDCFs), mainly represented by oxygen free radicals, is now viewed as an important mechanism causing atherothrombosis. Data in humans indicate that endogenous estrogen plays a protective role on endothelial function. Thus premenopausal women are protected against the adverse effect of hypercholesterolemia, with age-related impairment of endothelial function occurring only after the menopause in normotensive women and mainly after the menopause in hypertensive women. Moreover endogenous estrogen deprivation selectively impairs endothelial function in normotensive women. There is also evidence that exogenous estrogen can improve endothelial function in postmenopausal women. Thus acute intraarterial or intravenous infusion of estrogen potentiates endothelium-dependent vasodilation both in coronary circulation and the forearm. Estrogen replacement therapy (ERT) seems to improve endothelial function both in coronary arteries of postmenopausal women with coronary atherosclerosis and in brachial arteries of postmenopausal women with mild hypercholesterolemia. Although short-term ERT did not improve endothelial function in the forearm of perimenopausal women and in postmenopausal women with various cardiovascular risk factors, 3-month ERT restored endothelial function in ovariectomized women.

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References

  1. Gerhard M, Ganz P. How do we explain the clinical benefits of estrogen? From bedside to bench. Circulation 1995;92:5–8

    PubMed  CAS  Google Scholar 

  2. Grodstein F, Stampfer MJ, Manson JE, et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996;335:453–61.

    Article  PubMed  CAS  Google Scholar 

  3. Bush TL, Barrett-Connor E, Cowan LD, et al. Cardiovascular mortality and noncontraceptive estrogen use in women: Results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987;75:1102–9.

    PubMed  CAS  Google Scholar 

  4. Sack MN, Rader DJ, O Cannon R III. Ostrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet 1994;343:269–70.

    Article  PubMed  CAS  Google Scholar 

  5. Adams MR, Kaplan JR, Manuck SB, et al. Inhibition of coronary artery atherosclerosis by 17β-estradiol in ovariectomized monkeys: Lack of an effect of added progesterone. Arteriosclerosis 1990;10:1051–57.

    PubMed  CAS  Google Scholar 

  6. Luscher TF, Vanhoutte PM. The endothelium: Modulator of cardiovascular function. Boca Raton, Florida: CRC Press, 1990: 1–215.

    Google Scholar 

  7. Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:424–526.

    Article  Google Scholar 

  8. Furchgott RF. Role of endothelium in response of vascular smooth muscle. Circ Res 1983; 53:557–73.

    PubMed  CAS  Google Scholar 

  9. De Mey JG, Vanhoutte PM. Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries. J Physiol 1981;316:347–55.

    PubMed  Google Scholar 

  10. Luscher TF, Cooke JP, Houston DS, Neves R, Vanhoutte PM. Endothelium-dependent relaxations in human arteries. Mayo Clin Proc 1987;62:601–6.

    PubMed  CAS  Google Scholar 

  11. Luscher TF, Diederich D, Siebenmann R, Lehmann K, et al. Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts. N Engl J Med 1988;319:462–67.

    Article  PubMed  CAS  Google Scholar 

  12. Luscher TF, Vanhoutte PM. Endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats. Hypertension 1986;8:344–48.

    PubMed  CAS  Google Scholar 

  13. Diederich D, Yang Z, Buhler FR, Luscher TF. Impaired endothelium-dependent relaxations in hypertensive resistance arteries involve the cyclooxygenase pathway. Am J Physiol 1990;258:H445–H451.

    PubMed  CAS  Google Scholar 

  14. Shirahase H, Fujiwara M, Usui H, Kurahashi K. A possible role of thromboxane A2 in endothelium in maintaining resting tone and producing contractile response to acetylcholine and arachidonic acid in canine cerebral artery. Blood Vessels 1987;24:117–19.

    PubMed  CAS  Google Scholar 

  15. Kato T, Iwama Y, Okumura K, Hashimoto H, Ito T, Satake T. Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. Hypertension 1990;15:475–82.

    PubMed  CAS  Google Scholar 

  16. Katusic ZS, Vanhoutte PM. Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 1989;257:H33–H37.

    PubMed  CAS  Google Scholar 

  17. Taddei S, Virdis A, Ghiadoni L, Salvetti A. Hypertension and endothelial dysfunction. Cardiovasc Risk Factors 1997;7:76–87.

    Google Scholar 

  18. Rosselli M, Imthurn B, Macas E, Keller PJ, Dubey RK. Circulating nitrite/nitrate levels increase with follicular development: Indirect evidence for estradiol mediated NO-release. Biochem Biophys Res Commun 1994;202:1543–52.

    Article  PubMed  CAS  Google Scholar 

  19. Hashimoto M, Akishita M, Eto M, et al. Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation 1995; 92:3431–35.

    PubMed  CAS  Google Scholar 

  20. Casino PR, Kilcoyne CM, Quyyumi AA, Hoeg JM, Panza JA. The role of nitric-oxide in endothelium-dependent vasodilation of hypercholesterolemic patients. Circulation 1993; 88:2541–47.

    PubMed  CAS  Google Scholar 

  21. Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and essential hypertensive patients. Circulation 1995;91:1981–87.

    PubMed  CAS  Google Scholar 

  22. Taddei S, Virdis A, Mattei P, et al. Hypertension causes premature aging of endothelial function in humans. Hypertension 1997, 29:736–43.

    PubMed  CAS  Google Scholar 

  23. Chowienczyk PJ, Watts GF, Cockcroft JR, et al. Sex differences in endothelial function in normal and hypercholesterolemic subjects. Lancet 1994;344:305–6.

    Article  PubMed  CAS  Google Scholar 

  24. Furchgott RF, Zawadzky JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–76.

    Article  PubMed  CAS  Google Scholar 

  25. Celermajer DS, Sorensen, KE, Spielgelhalter DJ, Geogakopoulos D, Robinson J, Deanfield JE. Aging is associated with endothelial dysfunction in healthy men years before the age related decline in women. J Am Coll Cardiol 1994;24:471–76.

    Article  PubMed  CAS  Google Scholar 

  26. Taddei S, Virdis A, Ghiadoni L, et al. Menopause is associated with endothelial dysfunction in women. Hypertension 1996;28:576–82.

    PubMed  CAS  Google Scholar 

  27. Pinto S, Virdis A, Ghiadoni L, et al. Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women. Hypertension 1997;29:576–82.

    Google Scholar 

  28. Sorensen KE, Dorup I, Hermann AP, Mosekilde L. Combined hormone replacement therapy does not protect women against the age-related decline in endothelium-dependent vasomotor function. Circulation 1998;97:1234–38.

    PubMed  CAS  Google Scholar 

  29. McCrohon JA, Adams MR, McCredie RJ, et al. Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women. Clin Endocrinol 1996;45:435–41.

    Article  CAS  Google Scholar 

  30. Gilligan DM, Quyyumi AA, Cannon III RO. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation 1994;89:2545–51.

    PubMed  CAS  Google Scholar 

  31. Gilligan DM, Badar DM, Panza JA, Quyyumi AA, Cannon III RO. Acute vascular effects of estrogen in postmenopausal women. Circulation 1994;90:786–91.

    PubMed  CAS  Google Scholar 

  32. Tagawa H, Shimokawa H, Tagawa T, Matsumoto MK, Hirooka Y, Takeshita A. Shortterm estrogen augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilation in postmenopausal women. J Cardiovasc Pharmacol 1997;30:481–88.

    Article  PubMed  CAS  Google Scholar 

  33. Herrington DM, Braden GA, Williams JK, Morgan TM. Endothelial-dependent coronary vasomotor responsiveness in postmenopausal women with and without estrogen replacement therapy. Am J Cardiol 1994;73:951–52.

    Article  PubMed  CAS  Google Scholar 

  34. Lieberman EH, Gerhard MD, Uehata A, et al. Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Ann Intern Med 1994;121:936–41.

    PubMed  CAS  Google Scholar 

  35. Sudhir K, Jennings GL, Funder JW, Komesaroff PA. Estrogen enhances basal nitric oxide release in the forearm vasculature in perimenopausal women. Hypertension 1996;28:330–34.

    PubMed  CAS  Google Scholar 

  36. Lyons D, Webster J, Benjamin N. The effect of antihypertensive therapy on responsiveness to local intra-arterial NG-monomethyI-L-arginine in patients with essential hypertension. J Hypertens 1994;12:1047–52.

    PubMed  CAS  Google Scholar 

  37. Gilligan DM, Badar DM, Panza JA, Quyyumi AA, Cannon III RO. Effects of estrogen replacement therapy on peripheral vasomotor function in postmenopausal women. Am J Cardiol 1995;75:264–68.

    Article  PubMed  CAS  Google Scholar 

  38. Rosselli M, Imthurn B, Keller PJ, Jackson EK, Dubey RK. Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 β-estradiol and norethisterone acetate. Hypertension 1995;25 [part2]:848–53.

    PubMed  CAS  Google Scholar 

  39. Reis SE, Gloth ST, Blumenthal RS, et al. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation 1994;89:52–60.

    PubMed  CAS  Google Scholar 

  40. Kawano H, Motoyama T, Kugiyama K, et al. Gender difference in improvement of endothelium-dependent vasodilation after estrogen supplementation. J Am Coll Cardiol 1997;30:914–19.

    Article  PubMed  CAS  Google Scholar 

  41. New G, Timmins K, Duffy S, et al. Long-term estrogen therapy improves vascular function in male to female transsexuals. J Am Coll Cardiol 1997;29:1437–44.

    Article  PubMed  CAS  Google Scholar 

  42. McCrohon JA, Walters W, Robinson J, et al. Arterial reactivity is enhanced in genetic males taking high dose estrogens. J Am Coll Cardiol 1997;29:1432–36.

    Article  PubMed  CAS  Google Scholar 

  43. Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sei USA 1994;91:5212–16.

    Article  CAS  Google Scholar 

  44. Keaney JF, Shwaery GT, Xu A, et al. 17β-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine. Circulation 1994;89:2251–59.

    PubMed  CAS  Google Scholar 

  45. Pinto S, Virdis A, Ghiadoni L, et al. Mechanisms responsible for endothelial dysfunction associated to acute estrogen deprivation in normotensive women (abstract). Eighth European Meeting on Hypertension, Milan, 1997.

    Google Scholar 

  46. Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 1998;97;2222–29.

    PubMed  CAS  Google Scholar 

  47. Vogel RA and Corretti MC. Estrogens, progestins, and heart disease. Circulation 1998;97: 1223–26.

    PubMed  CAS  Google Scholar 

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© 1999 Kluwer Academic Publishers and Fondazione Giovanni Lorenzini

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Virdis, A., Ghiadoni, L., Sudano, I., Pinto, S., Taddei, S., Salvetti, A. (1999). Estrogen and Endothelial Function. In: Women’s Health and Menopause. Medical Science Symposia Series, vol 13. Springer, Dordrecht. https://doi.org/10.1007/978-0-585-37973-9_13

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  • DOI: https://doi.org/10.1007/978-0-585-37973-9_13

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-5906-7

  • Online ISBN: 978-0-585-37973-9

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