β-adrenergic receptors and receptor signaling in heart failure

Cardiac beta-adrenergic receptors, which respond to neuronally released and circulating catecholamines, are important regulators of cardiac function. Congestive heart failure, a common clinical condition, is associated with a number of alterations in the activation and deactivation of beta-adrenergic receptor pathways. Studies with failing hearts from humans and animals indicate that such alterations include changes in the expression or function of beta-adrenergic receptors, G-proteins, adenylyl cyclases, and G-protein receptor kinases. The net effect of these alterations is the substantial blunting of beta-adrenergic receptor-mediated cardiac response. An important unanswered question is whether the loss of cardiac beta-adrenergic receptor responsiveness is a contributing cause, or a result, of ventricular dysfunction. Even though this question remains unanswered, the concept of targeting the beta-adrenergic pathway in the failing heart is becoming increasingly popular and several new therapeutic strategies are in development.