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β-Adrenergic Receptor Signaling in Heart Failure

  • Grace Jung Ah Lee
  • Lin Yan
  • Dorothy E. Vatner
  • Stephen F. Vatner
Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 5)

Abstract

Acute activation of the sympathetic system and resultant β-adrenergic receptor (β-AR) signaling are required to maintain homeostasis, providing inotropic support in times of need, as in “fight or flight” or response to any stress, such as cardiac dysfunction and heart failure. For most of the twentieth century, it was reasoned that sympathetic stimulation of β-ARs through administration of naturally occurring catecholamines or synthetic sympathomimetic amines could provide inotropic support and should be used in heart failure therapy. However, in heart failure, sympathetic drive to the heart is excessively increased, and chronic sympathetic stimulation is deleterious, since it increases \( \text{M}\text{ {0.05em}}\stackrel{·}{\text{V}}\text{ {0.05em}}{\text{O}}_{2} \), which cannot be met by appropriate increases in coronary blood flow, thereby creating subendocardial ischemia and intensifying the cardiac dysfunction. Furthermore, continued stimulation of the β-ARs also becomes problematic because it can activate multiple cellular processes including those involved in pathological remodeling seen in the development of cardiomyopathy. However, this reasoning took a diametrically opposite turn in the latter twentieth century when the adverse effects of chronic β-AR stimulation became apparent from experimental studies in transgenic mice with cardiac-specific overexpression of G and β-ARs and also from clinical studies with poor outcomes for patients on chronic sympathomimetic amine therapy. At this time it was also found that internal compensatory physiological processes countering continued β-AR stimulation in the heart were cleverer than physicians. As a protective response, β-AR desensitize, which reduces the effectiveness of β-AR stimulation and the consequent increases in myocardial oxygen demands. Taken together, these factors were fundamental to the change in course from β-AR stimulation to β-AR blockade in the treatment of heart failure.

Keywords

β-Adrenergic receptor Inotropic agonist β-Adrenergic receptor blockers Desensitization 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Grace Jung Ah Lee
    • 1
  • Lin Yan
    • 1
  • Dorothy E. Vatner
    • 1
  • Stephen F. Vatner
    • 1
  1. 1.Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical SchoolUniversity of Medicine and Dentistry of New JerseyNewarkUSA

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