The use of beta3-adrenergic receptor agonists in the treatment of heart failure.

As the beta3-adrenergic receptor (beta3-AR) mediates a negative inotropic effect, upregulation of this receptor in patients with heart failure is considered to be harmful and associated with disease progression. The development of beta3-AR antagonists has therefore been proposed as a potential therapeutic option for heart failure. However, as increased intracellular myocyte Na+ levels represent a key adverse pathophysiological feature of heart failure, and the beta3-AR mediates the stimulation of the only export route for Na+ - the Na+-K+ pump - the upregulation of this receptor may also represent a useful compensatory mechanism. Data from animal studies and circumstantial observations from clinical trials suggest that beta3-AR activation is beneficial in severe heart failure, and that beta3-AR agonists are a promising therapeutic option for the treatment of this disease.