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Article
Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle
American Journal of Physiology - Heart and Circulatory Physiology
  • Richard E. White
  • Guichun Han
  • Christiana Dimitropoulou
  • Shu Zhu, Philadelphia College of Osteopathic Medicine
  • Katsuya Miyake
  • David Fulton
  • Shaylee Dave
  • Scott A. Barman
Document Type
Article
Publication Date
1-1-2005
Abstract
Although previous studies demonstrated beneficial effects of estrogen on cardiovascular function, the Women's Health Initiative has reported an increased incidence of coronary heart disease and stroke in post-menopausal women taking hormone replacement therapy. The objective of the present study was to identify a molecular mechanism whereby estrogen, a vasodilatory hormone, could possibly increase the risk of cardiovascular disease. Isometric contractile force recordings were performed on endothelium-denuded porcine coronary arteries, whereas molecular and fluorescence studies identified estrogen signaling molecules in coronary smooth muscle. Estrogen (1-1,000 nM) relaxed arteries in an endothelium-independent fashion; however, when arteries were pretreated with agents to uncouple nitric oxide (NO) production from NO synthase (NOS), estrogen contracted coronary arteries with an EC50 of 7.3 ± 4 nM. Estrogen-induced contraction was attenuated by reducing superoxide (O 2-). Estrogen-stimulated O2- production was detected in NOS-uncoupled coronary myocytes. Interestingly, only the type 1 neuronal NOS isoform (nNOS) was detected in myocytes, making this protein a likely target mediating both estrogen-induced relaxation and contraction of endothelium-denuded coronary arteries. Estrogen-induced contraction was completely inhibited by 1 μM nifedipine or 10 μM indomethacin, indicating involvement of dihydropyridine-sensitive calcium channels and contractile prostaglandins. We propose that a single molecular mechanism can mediate the dual and opposite effect of estrogen on coronary arteries: by stimulating type 1 nNOS in coronary arteries, estrogen produces either vasodilation via NO or vasoconstriction via O2-. Copyright © 2005 the American Physiological Society.
Comments

This article was published in American Journal of Physiology - Heart and Circulatory Physiology, Volume 289, Issue 4 58-4, Pages H1468-H1475.

The published version is available at http://dx.doi.org/10.1152/ajpheart.01173.2004.

Copyright © 2005 Scopus.

Citation Information
Richard E. White, Guichun Han, Christiana Dimitropoulou, Shu Zhu, et al.. "Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle" American Journal of Physiology - Heart and Circulatory Physiology Vol. 289 Iss. 4 58-4 (2005) p. H1468 - H1475
Available at: http://works.bepress.com/richard_white/14/