β3-Adrenergic stimulation in the human heart:: Signal transduction, functional implications and therapeutic perspectives

Next to beta(1)- and beta(2)-adrenoceptors, a third beta-adrenoceptor population is expressed in the human heart, the beta(3)-adrenoceptor. In mammalian ventricular myocytes, beta(3)-adrenergic stimulation leads to a decrease in contractility via a release of nitric oxide (NO). Recently, different molecular mechanisms of beta(3)-adrenergic activation of endothelial nitric oxide synthase (eNOS) have been uncovered in cardiac myocytes. In the non-failing and especially the failing heart, beta(3)-adrenergic stimulation may offer protection against excessive catecholaminergic beta(1)-adrenoceptor stimulation. In this context, the beta(3)-adrenoceptor is discussed as a novel target for the pharmacological therapy of heart failure.