The role of beta-adrenergic receptors in heart failure: Differential regulation of cardiotoxicity and cardioprotection

beta-adrenergic receptor blockers have demonstrated significant survival benefit and have become standard therapy for adults with dilated cardiomyopathy, although their efficacy in pediatric patients is still unproven. Recent data suggests that the two major cardiac beta-adrenergic receptor subtypes ( beta 1 and beta 2) couple differentially to intracellular signaling pathways regulating contractility and remodeling. This has led some to suggest that the beta 1 receptor is the cardiotoxic subtype whereas the beta 2 receptor is cardioprotective. Given this paradigm, there could be situations where subtype selective beta-blockade or even subtype selective beta-stimulation might be beneficial. However, since most of these studies have been performed in isolated cardiomyocytes, their application to clinical practice is unclear. To better understand the roles of beta 1- vs. beta 2- receptors in the pathogenesis of clinical cardiomyopathy, we and others have taken advantage of several well-characterized murine models of cardiovascular disease. These studies demonstrate that beta-receptor regulation of the balance between cardioprotection and cardiotoxicity is even more complex than previously appreciated: the role of each beta-receptor subtype may vary depending on the specific cardiac stressor involved (e.g. ischemia, pressure overload, genetic mutation, cardiotoxin). Furthermore, the remodeling effects of beta-receptor signaling have a temporal component, depending on whether a cardiac stress is acute vs. chronic. (C) 2010 Elsevier Ireland Ltd. All rights reserved.