Myocardial beta-adrenergic receptor signaling in vivo: Insights from transgenic mice

Heart failure is a problem of increasing importance in cardiovascular medicine. An important characteristic of heart failure is reduced agonist-stimulated adenylyl cyclase activity (receptor desensitization) due to both diminished receptor number (receptor downregulation) and impaired receptor function (receptor uncoupling). These changes in the -adrenergic receptor (-AR) system may in part account for some of the abnormalities of contractile function in this disease. Myocardial contraction is closely regulated by G protein coupled beta-adrenergic receptors through the action of the second messenger cAMP. The beta-adrenergic receptors themselves are regulated by a set of specific kinases, termed the G-protein-coupled receptor kinases. The study of this complex system in vive has recently been advanced by the development of transgenic and gene targeted (''knock-out'') mouse models. Combining transgenic technology with sophisticated physiological measurements of cardiac hemodynamics is an extremely powerful strategy to study the regulation of myocardial contractility in the normal and failing heart.