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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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287, F586-F591
|Abstract »|Full Text »|PDF »
Gender modulates cardiac phenotype development in genetically modified mice.
A New Slice of Pie?: Estrogen Regulation of Plasminogen Activator Inhibitor-1.
N. Madamanchi, X. Liu, and M. S. Runge (2004)
Circ. Res.
95, 228-229
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Endothelium-Dependent and Independent Enhancement of Vascular Contractility in the Ovariectomized Rabbit.
M. Koga, K. Hirano, J. Nishimura, H. Nakano, and H. Kanaide (2004)
Reproductive Sciences
11, 272-279
|Abstract »|PDF »
The G Protein-coupled Receptor GPR30 Mediates c-fos Up-regulation by 17{beta}-Estradiol and Phytoestrogens in Breast Cancer Cells.
M. Maggiolini, A. Vivacqua, G. Fasanella, A. G. Recchia, D. Sisci, V. Pezzi, D. Montanaro, A. M. Musti, D. Picard, and S. Ando (2004)
J. Biol. Chem.
279, 27008-27016
|Abstract »|Full Text »|PDF »
Differential Regulation of Estrogen Receptor Subtypes {alpha} and {beta} in Human Aortic Smooth Muscle Cells by Oligonucleotides and Estradiol.
F. Barchiesi, E. K. Jackson, B. Imthurn, J. Fingerle, D. G. Gillespie, and R. K. Dubey (2004)
J. Clin. Endocrinol. Metab.
89, 2373-2381
|Abstract »|Full Text »|PDF »
Aberrant Cholesterol Transport and Impaired Steroidogenesis in Leydig Cells Lacking Estrogen Sulfotransferase.
M. H. Tong, L. K. Christenson, and W.-C. Song (2004)
Endocrinology
145, 2487-2497
|Abstract »|Full Text »|PDF »
Gender, sex hormones, and vascular tone.
J. M. Orshal and R. A. Khalil (2004)
Am J Physiol Regulatory Integrative Comp Physiol
286, R233-R249
|Abstract »|Full Text »|PDF »
Hormonal Regulation of Normal Vascular Tone in Males.
M. E. Mendelsohn and G. M.C. Rosano (2003)
Circ. Res.
93, 1142-1145
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Impaired Acetylcholine-Induced Release of Nitric Oxide in the Aorta of Male Aromatase-Knockout Mice: Regulation of Nitric Oxide Production by Endogenous Sex Hormones in Males.
M. Kimura, K. Sudhir, M. Jones, E. Simpson, A.-M. Jefferis, and J. P.F. Chin-Dusting (2003)
Circ. Res.
93, 1267-1271
|Abstract »|Full Text »|PDF »
Regulation of nitric oxide-dependent vasodilation in coronary arteries of estrogen receptor-{alpha}-deficient mice.
J. M. Muller-Delp, D. B. Lubahn, K. E. Nichol, B. J. Philips, E. M. Price, E. M. Curran, and M. H. Laughlin (2003)
Am J Physiol Heart Circ Physiol
285, H2150-H2157
|Abstract »|Full Text »|PDF »