Effect of alpha1-adrenergic receptors in cardiac pathophysiology.
Compelling evidence now exists that proves adrenergic blockade is at the center of neurohormonal antagonism in heart failure (HF). Catecholamines are well known to act through both beta- and alpha-adrenergic receptors (ARs), which mediate their effects through distinct receptor pathways. Beta-AR blockers are commonly used in the treatment of HF and have distinct receptor affinity profiles. The recent COMET trial comparing 2 important beta-blocking drugs showed a distinct advantage for carvedilol in decreasing the risk of mortality from HF. The mechanism of action for carvedilol differs from metoprolol tartrate in its ability to block both alpha- and beta-ARs, leading to renewed interest in the potential role of alpha-ARs in the progression of HF. In contrast, however, the ALLHAT study discontinued use of doxazosin, an alpha1-receptor blocker because of an increase in cardiovascular events among patients using this drug. The results of these studies appear to be in contrast with respect to the role of alpha-ARs in regards to cardiovascular pathophysiology. Further study of the alpha-receptor and understanding the role of alpha-ARs in HF is necessary to understand the therapeutic effect of alpha-blockade. This article reviews our understanding of the alpha-AR in HF.
Shannon
Richard
R
Allegheny General Hospital, University School of Medicine, Pittsburgh, PA 15212, USA.
Chaudhry
Mohammad
M
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002986:Clinical Trials as Topic; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006984:Hypertrophy; D050356:Lipid Metabolism; D051379:Mice; D017202:Myocardial Ischemia / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000473:pathology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D005947:Glucose