Adrenergic and muscarinic receptor regulation and therapeutic implications in heart failure.

In end-stage heart failure the expression of different myocardial regulatory proteins involved in the beta-adrenergic cAMP signalling pathway is altered. The downregulation of beta 1-adrenoceptors and their uncoupling from the effector as well as an increased expression of the inhibitory GTP-binding protein seem to be the most important alterations. Since catecholamine levels are elevated in these patients and since some alterations can be 'restored' after treatment with beta-adrenoceptor antagonists it was hypothesized that excessive beta-adrenergic stimulation could be involved in these alterations. In this article the changes of beta-adrenergic receptors, GTP-binding proteins, sarcoplasmic reticulum Ca(2+)-ATPase and of phospholamban found in heart failure are addressed with its possible therapeutic implications.