Cardiac β3-adrenoceptors-A role in human pathophysiology?

As beta(3)-adrenoceptors were first demonstrated to be expressed in adipose tissue they have received much attention for their metabolic effects in obesity and diabetes. After the existence of this subtype had been suggested to be present in the heart, studies focused on its role in cardiac function. While the presence and functional role of beta(3)-adrenoceptors in the heart has not uniformly been detected, there is a broad consensus that they become up-regulated in pathological conditions associated with increased sympathetic activity such as heart failure and diabetes. When detected, the beta(3)-adrenceptor has been demonstrated to mediate negative inotropic effects in an inhibitory G protein-dependent manner through the NO-cGMP-PKG signalling pathway. Whether these negative inotropic effects provide protection from the adverse effects induced by overstimulation of beta(1)/beta(2)-adrenoceptors or in themselves are potentially harmful is controversial, but ongoing clinical studies in patients with congestive heart failure are testing the hypothesis that beta(3)-adrenceptor agonism has a beneficial effect.