Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta.
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 beta (ERbeta)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERbeta-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERbeta-deficient mice. Vascular smooth muscle cells isolated from ERbeta-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERbeta-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERbeta in the regulation of vascular function and blood pressure.
Zhu
Yan
Y
Molecular Cardiology Research Institute, New England Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.
Bian
Zhao
Z
Lu
Ping
P
Karas
Richard H
RH
Bao
Lin
L
Cox
Daniel
D
Hodgin
Jeffrey
J
Shaul
Philip W
PW
Thoren
Peter
P
Smithies
Oliver
O
Gustafsson
Jan-Ake
JA
Mendelsohn
Michael E
ME
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001794:Blood Pressure; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D000077267:Fulvestrant; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D019335:Nitroarginine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006146:Guanidines; D015221:Potassium Channels; D011960:Receptors, Estrogen; D010656:Phenylephrine; D019335:Nitroarginine; D000077267:Fulvestrant; D004958:Estradiol; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine