title: Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice.
abstract: alpha(2A)-Adrenergic receptors (ARs) in the midbrain regulate sympathetic nervous system activity, and both alpha(2A)-ARs and alpha(2C)-ARs regulate catecholamine release from sympathetic nerve terminals in cardiac tissue. Disruption of both alpha(2A)- and alpha(2C)-ARs in mice leads to chronically elevated sympathetic tone and decreased cardiac function by 4 mo of age. These knockout mice have increased mortality, reduced exercise capacity, decreased peak oxygen uptake, and decreased cardiac contractility relative to wild-type controls. Moreover, we observed significant abnormalities in the ultrastructure of cardiac myocytes from alpha(2A)/alpha(2C)-AR knockout mice by electron microscopy. Our results demonstrate that chronic elevation of sympathetic tone can lead to abnormal cardiac function in the absence of prior myocardial injury or genetically induced alterations in myocardial structural or functional proteins. These mice provide a physiologically relevant animal model for investigating the role of the sympathetic nervous system in the development and progression of heart failure.
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
authors.forename: Jon
authors.initials: J
authors.lastname: Kosek
authors.forename: Andrew
authors.initials: A
authors.lastname: Patterson
authors.forename: Daniel
authors.initials: D
authors.lastname: Bernstein
authors.forename: Brian
authors.initials: B
authors.lastname: Kobilka
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D005082:Physical Exertion; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D018341:Receptors, Adrenergic, alpha-2