Mechanisms of abnormal transmembrane signaling of the β-adrenergic receptor in congestive heart failure
Receptors, Adrenergic, beta
Congestive heart failure is associated with blunted cardiac adrenergic responsiveness, clinically manifested by diminished chronotropic, inotropic, and lusitropic responses to beta-adrenergic stimulation. Recent advances in our understanding of the multiple components of the beta-adrenergic receptor complex and of the mechanisms by which these components interact with each other have led to insights beyond the mere evaluation of beta-receptors to account for adrenergic hyporesponsiveness in congestive heart failure. In addition to a reduction in beta-adrenergic receptors, the failing heart appears to show key abnormalities in the guanine nucleotide-binding proteins that link the beta-receptor to its biochemical effector. A reduction in the stimulatory protein and in the extent to which the stimulatory protein is linked to the beta-receptor are demonstrable in peripheral circulating lymphocytes and in cardiac tissue. These abnormalities are at least partially reversible.