Mechanisms of abnormal transmembrane signaling of the beta-adrenergic receptor in congestive heart failure.
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.
Horn
E M
EM
Columbia Univeristy College of Physicians and Surgeons, Department of Medicine, New York, NY 10032.
Bilezikian
J P
JP
D000262:Adenylyl Cyclases / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D019204:GTP-Binding Proteins / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013566:Sympathomimetics / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases