Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β

Author:

Zhu Yan1,Bian Zhao23,Lu Ping1,Karas Richard H.1,Bao Lin1,Cox Daniel1,Hodgin Jeffrey4,Shaul Philip W.5,Thorén Peter3,Smithies Oliver4,Gustafsson Jan-Åke2,Mendelsohn Michael E.1

Affiliation:

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.

Abstract

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 β (ERβ)–deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERβ-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERβ in the regulation of vascular function and blood pressure.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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