Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor 
Yan Zhu,1
Zhao Bian,23
Ping Lu,1
Richard H. Karas,1
Lin Bao,1
Daniel Cox,1
Jeffrey Hodgin,4
Philip W. Shaul,5
Peter Thorén,3
Oliver Smithies,4
Jan-Åke Gustafsson,2
Michael E. Mendelsohn1*
Blood vessels express estrogen receptors, but their role
in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor 
(ER)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ER-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood
vessels from ER-deficient mice. Vascular smooth muscle cells
isolated from ER-deficient mice show multiple abnormalities of ion
channel function. Furthermore, ER-deficient mice develop sustained
systolic and diastolic hypertension as they age. These data support an
essential role for ER in the regulation of vascular function 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
