We studied alterations in the -adrenergic receptor (-AR) system of rabbit hearts during the development of heart failure (HF) after myocardial infarction (MI) to determine whether the molecular -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 -AR signaling was examined in tissue and cultured ventricular myocytes. We found that there was a significant global reduction in -AR density by ~50% in both ventricles of MI animals compared with sham-operated control animals and that functional -AR coupling was significantly reduced. Importantly, as found in human HF, myocardial protein levels and activity of the -AR kinase (-ARK1) and G_i were found to be significantly elevated in MI rabbits, suggesting that these molecules are contributing to myocardial dysfunction. Thus the myocardial -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.

myocardial infarction; -adrenergic receptor desensitization; G protein signaling; -adrenergic receptor kinase; heart failure; -adrenergic receptor

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