Beta₃-adrenergic receptors in the heart: Normal functions and potential roles in heart failure

Abstract

Heart Failure is the state in which the heart is unable to pump enough blood to meet the needs of the body, resulting from events that progressively damage the myocardium and/or its ability to contract normally. Several compensatory mechanisms allow for short-term maintenance of adequate delivery of blood to the body. Progression from the initial events to heart failure is caused by the accumulation of pathologic changes and their effects, many of which result from chronic activation of these compensatory mechanisms. One of these mechanisms is the activation of the neurohormonal β-adrenergic system, to which the β₃-adrenergic receptor (β₃-AR) belongs. Research on the role of the β₃-AR in the heart has focused on the short-term protective role of the receptor, based on its ability to reduce the effects of over-stimulation of the heart's other adrenergic-system components. However, during the course of heart failure, its up-regulation and functional persistence may also contribute to the progression of the disease. There have been few large-animal studies, no human trials, and no long-term studies of β₃-AR agonists for use in the treatment of heart failure. Ultimately, individualized treatment strategies that, over time, modulate the relative levels of agonistic and antagonistic effects across each of the three β₃-AR subtypes, may be most effective for management of heart failure. However, further research and trials with β₃-AR agonists are realistic and necessary places to start.