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Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor
Yan Zhu,1Zhao Bian,23Ping Lu,1Richard H. Karas,1Lin Bao,1Daniel Cox,1Jeffrey Hodgin,4Philip W. Shaul,5Peter Thorén,3Oliver Smithies,4Jan-Åke Gustafsson,2Michael E. Mendelsohn1*
Blood vessels express estrogen receptors, but their role
in cardiovascular physiology is not well understood. We show thatvascular smooth muscle cells and blood vessels from estrogen receptor (ER)-deficient mice exhibit multiple functional abnormalities.In wild-type mouse blood vessels, estrogen attenuates vasoconstrictionby an ER-mediated increase in inducible nitric oxide synthaseexpression. In contrast, estrogen augments vasoconstriction inblood
vessels from ER-deficient mice. Vascular smooth musclecells
isolated from ER-deficient mice show multiple abnormalitiesof ion
channel function. Furthermore, ER-deficient mice developsustained
systolic and diastolic hypertension as they age. Thesedata support an
essential role for ER in the regulation of vascularfunction and
blood pressure.
1 Molecular Cardiology Research Institute, New
England Medical Center and Department of Medicine, Tufts University
School of Medicine, Boston, MA 02111, USA.
2 Department of Medical Nutrition and Center for
Biotechnology, Novum, Huddinge University Hospital, 141 86 Huddinge,
Sweden.
3 Department of Physiology and Pharmacology,
171 77, Karolinska Institute, Stockholm, Sweden.
4 Department of Pathology, University of North
Carolina, Chapel Hill, NC 27599, USA.
5 Department
of Pediatrics, University of Texas Southwestern Medical Center, Dallas,
TX 75390, USA.
*
To whom correspondence should be addressed. E-mail:
mmendelsohn{at}lifespan.org
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Nonnuclear Actions of Estrogen.
K. J. Ho and J. K. Liao (2002)
Arterioscler Thromb Vasc Biol
22, 1952-1961
|Abstract »|Full Text »|PDF »
Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium.
C. Forster, S. Makela, A. Warri, S. Kietz, D. Becker, K. Hultenby, M. Warner, and J.-A. Gustafsson (2002)
PNAS
99, 15578-15583
|Abstract »|Full Text »|PDF »
The Atheroprotective Effect of Dietary Soy Isoflavones in Apolipoprotein E-/- Mice Requires the Presence of Estrogen Receptor-{alpha}.
M. R. Adams, D. L. Golden, T. C. Register, M. S. Anthony, J. B. Hodgin, N. Maeda, and J.K. Williams (2002)
Arterioscler Thromb Vasc Biol
22, 1859-1864
|Abstract »|Full Text »|PDF »
Estrogen Receptors {alpha} and {beta} Have Similar Activities in Multiple Endothelial Cell Pathways.
M. J. Evans, H. A. Harris, C. P. Miller, S. K. Karathanasis, and S. J. Adelman (2002)
Endocrinology
143, 3785-3795
|Abstract »|Full Text »|PDF »
Clues to understanding the role of estrogen receptors in mediating cardiovascular protection.
(ER
