beta-adrenergic receptor regulation and left ventricular function in idiopathic dilated cardiomyopathy.
Alterations in the myocardial receptor-G protein-adenylate cyclase (RGC) complex and cardiac adrenergic neurons in the failing human heart result in subsensitivity to beta-adrenergic stimulation. Pharmacologic interventions such as beta blockade may modify critical components of the RGC complex and partially restore the sensitivity of the beta-adrenergic pathway. Among the receptors coupled to the stimulatory (Gs) protein are the beta 1 and beta 2 receptors. Because of differences in receptor population and agonist (i.e., norepinephrine) affinity, the beta 1-receptor is the predominate adrenergic subtype regulating contractility in the nonfailing myocardium. Down-regulation occurs in the myocardial beta-receptor component of the RGC complex with mild-to-moderate and severe left ventricular dysfunction. However, abnormalities of the RGC complex vary with the etiology of heart failure; beta 1-receptor down-regulation is greater in idiopathic dilated cardiomyopathy than in post-infarction cardiomyopathy, while beta-receptor uncoupling is greater in post-infarction disease. In chronic heart failure, the adrenergic nervous system is activated in the heart and kidney. There is evidence that an increased cardiac norepinephrine concentration contributes to the decrease in beta 1-receptor density in heart failure. However, norepinephrine exposure is not the only factor responsible for regulating beta-adrenergic receptors in heart failure. Chronic beta blockade may improve hemodynamic and clinical response in patients with idiopathic dilated cardiomyopathy by protecting the myocardium from the cardiotoxic effects of increased catecholamines and by up-regulating the beta 1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Gilbert
E M
EM
Division of Cardiology, University of Utah School of Medicine, Salt Lake City 84132.
Olsen
S L
SL
Renlund
D G
DG
Bristow
M R
MR
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta