Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle

Richard E. White, Guichun Han, Christiana Dimitropoulou, Shu Zhu, Katsuya Miyake, David J Fulton, Shaylee Dave, Scott A Barman

Research output: Contribution to journalArticle

36 Citations (Scopus)

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-.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number4 58-4
DOIs
StatePublished - Oct 1 2005

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Vascular Smooth Muscle
Superoxides
Coronary Vessels
Estrogens
Nitric Oxide Synthase
Endothelium
Muscle Cells
Nitric Oxide
Protein Isoforms
Arteries
Hormone Replacement Therapy
Women's Health
Calcium Channels
Nifedipine
Vasoconstriction
Vasodilation
Indomethacin
Prostaglandins
Coronary Disease
Smooth Muscle

Keywords

  • Coronary circulation
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle. / White, Richard E.; Han, Guichun; Dimitropoulou, Christiana; Zhu, Shu; Miyake, Katsuya; Fulton, David J; Dave, Shaylee; Barman, Scott A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 4 58-4, 01.10.2005.

Research output: Contribution to journalArticle

White, Richard E. ; Han, Guichun ; Dimitropoulou, Christiana ; Zhu, Shu ; Miyake, Katsuya ; Fulton, David J ; Dave, Shaylee ; Barman, Scott A. / Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 289, No. 4 58-4.
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