Heart failure is arempanied by severely impaired adrenergic signal transduction fonction. At the receptor level, there is down-regulation of β1-adrenergic receptors and uncoupling of β2-adrenergic raptors. The latte has beed attributed to anincreased activity and gene expression of β-adrenergic receptor kinase in failing myocardium, leading to phosphorylation anduncoupling of receptors. In addition, an increase in inhibitory G protein α subunits (Gia) has been suggested to be causally linkedto the desensititaion of adenylyl cyclase and decrease in cyclic AMP (cAMP) accumulation. Recent evidence suggests thatcAMP-dependent transcription mechanisms may play a role during β-adrenergic stimulation and cardiompopathy with heartfailure by means of altered actions of cAMP response element binding protein. On the other hand, the role α1- adrenergic receptor in heart failure is somewhat controversial. The physiological significance of the α1-adrenergic receptor-G protein phospholipase C signaling pathway for the mediation of hypertrophic effects might be even higher than for the regulation ofcontractility in heart failure. The above findings indicate abnormal adrenergic signaling pathways in the pathogenesis of heartfailure and provide the potential therapy strategies that aim to restore the adrengic signal transduction function in failingmyocardium.
