Molecular β-adrenergic signaling abnormalities in failing rabbit hearts after infarction

John P. Maurice, Ashish S. Shah, Alan P. Kypson, Jonathan A. Hata, David C. White, Donald D. Glower, Walter J. Koch

Research output: Contribution to journalArticle

Abstract

We studied alterations in the β-adrenergic receptor (β-AR) system of rabbit hearts during the development of heart failure (HF) after myocardial infarction (MI) to determine whether the molecular β-AR abnormalities associated with human HF exist in this animal model. Rabbit HF was established 3 wk after left circumflex coronary artery (LCX) ligation by in vivo physiological measurements, and molecular β-AR signaling was examined in tissue and cultured ventricular myocytes. We found that there was a significant global reduction in β-AR density by ~50% in both ventricles of MI animals compared with sham-operated control animals and that functional β-AR coupling was significantly reduced. Importantly, as found in human HF, myocardial protein levels and activity of the β-AR kinase (β-ARK1) and Gα(i) were found to be significantly elevated in MI rabbits, suggesting that these molecules are contributing to myocardial dysfunction. Thus the myocardial β-AR system of this rabbit model of HF shares important biochemical characteristics with human HF and therefore is an ideal laboratory model to investigate novel therapeutic targets for the treatment of HF.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume276
Issue number6 45-6
StatePublished - Jun 1999
Externally publishedYes

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Keywords

  • β-adrenergic receptor
  • β-adrenergic receptor desensitization
  • β-adrenergic receptor kinase
  • G protein signaling
  • Heart failure
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Maurice, J. P., Shah, A. S., Kypson, A. P., Hata, J. A., White, D. C., Glower, D. D., & Koch, W. J. (1999). Molecular β-adrenergic signaling abnormalities in failing rabbit hearts after infarction. American Journal of Physiology - Heart and Circulatory Physiology, 276(6 45-6).