Molecular restoration of beta-adrenergic receptor signaling improves contractile function of failing hearts

beta-adrenergic receptor (betaAR) antagonists, or beta blockers, are now a part of the standard therapeutic arsenal in the medical management of chronic heart failure (HF). Conversely, betaAR stimulation remains the most efficient way to enhance cardiac contractile function acutely, although long-term inotropic therapy based on enhanced betaAR stimulation is likely detrimental. Although altered betaAR signaling plays a pivotal role in the genesis of HF, the choice to therapeutically agonize or antagonize this receptor pathway remains an area of ongoing investigation. Research from the authors' laboratory as well as other research conducted over the last 10 years has produced evidence to support the fact that "normalizing" the betaAR system at a molecular level and improving signaling, instead of blocking it, leads to significant enhancement of cardiac contractile function and prevents ventricular remodeling in HF. This review summarizes the extensive in vivo animal model experimentation that supports the still-controversial hypothesis that increasing the myocardial density of beta(2)-ARs or, more effectively, inhibiting the activity of the betaAR kinase (also referred to as G-protein-coupled receptor kinase 2), represent potential novel therapeutic strategies for HF.