[Adrenergic signal transduction in heart failure].
A review over adrenergic transmembrane signalling in human heart muscle cells, changes in this signalling in patients with heart failure and the influence of medical treatment of heart failure, is presented. In heart failure, the myocardial contractibility is decreased, although the plasma level of catecholamines is elevated. This can be due to changes in the transmembrane signalling. In heart failure, the numbers of beta-receptors are decreased, the amount of Gs-protein is probably unchanged and the amount of Gi-protein is probably increased. Changes in signalling are described in more detail in patients with heart failure based on idiopathic dilated cardiomyopathy (DCM), where a selective down regulation of beta 1-receptors is seen. In heart failure of other origin, there is probably a concomitant reduction in beta 1- and beta 2-receptors. The selective regulation in patients with DCM, can be based on autoantibodies. A 30% reduction in maximal response on selective beta 2 stimulation is additionally seen in patients with DCM, probably based on an increase in the amount of Gi-protein. beta-antagonists increase and beta-agonists decrease the numbers of beta-receptors. The regulation is selective when selective antagonists and agonists are used, and nonselective when nonselective drugs are used. How other drugs affect the transmembrane signalling is still to be elucidated.
Medicinsk/kardiologisk afdeling B, Odense Sygehus.
P
P
Ahlquist
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists
Adrenerg signaltransduktion ved hjertesvigt.