title: Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta.
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 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.
authors.affiliation: Molecular Cardiology Research Institute, New England Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Bian
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
authors.forename: Lin
authors.initials: L
authors.lastname: Bao
authors.forename: Daniel
authors.initials: D
authors.lastname: Cox
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hodgin
authors.forename: Philip W
authors.initials: PW
authors.lastname: Shaul
authors.forename: Peter
authors.initials: P
authors.lastname: Thoren
authors.forename: Oliver
authors.initials: O
authors.lastname: Smithies
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mendelsohn
mesh_terms: 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
chemical_list: 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