Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice

Patricia C. Brum, Jon Kosek, Andrew Patterson, Daniel Bernstein, Brian Kobilka

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

α2A-Adrenergic receptors (ARs) in the midbrain regulate sympathetic nervous system activity, and both α2A-ARs and α2C-ARs regulate catecholamine release from sympathetic nerve terminals in cardiac tissue. Disruption of both α2A- and α2C-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 α2A2C-AR knock-out 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.

Original languageEnglish (US)
Pages (from-to)H1838-H1845
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number5 52-5
StatePublished - Nov 1 2002

Fingerprint

Sympathetic Nervous System
Adrenergic Receptors
Knockout Mice
Mesencephalon
Cardiac Myocytes
Catecholamines
Electron Microscopy
Animal Models
Heart Failure
Oxygen
Mortality
Wounds and Injuries
Proteins

Keywords

  • Heart failure
  • Knockout mice
  • α-adrenergic receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Brum, P. C., Kosek, J., Patterson, A., Bernstein, D., & Kobilka, B. (2002). Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice. American Journal of Physiology - Heart and Circulatory Physiology, 283(5 52-5), H1838-H1845.

Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice. / Brum, Patricia C.; Kosek, Jon; Patterson, Andrew; Bernstein, Daniel; Kobilka, Brian.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 5 52-5, 01.11.2002, p. H1838-H1845.

Research output: Contribution to journalArticle

Brum, PC, Kosek, J, Patterson, A, Bernstein, D & Kobilka, B 2002, 'Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice', American Journal of Physiology - Heart and Circulatory Physiology, vol. 283, no. 5 52-5, pp. H1838-H1845.
Brum, Patricia C. ; Kosek, Jon ; Patterson, Andrew ; Bernstein, Daniel ; Kobilka, Brian. / Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2002 ; Vol. 283, No. 5 52-5. pp. H1838-H1845.
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