REVIEW ARTICLE
Beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors: shifting the focus from inotropy to cyclic adenosine monophosphate
Matthew A. Movsesian, MDa
a Salt Lake City VA Medical Center, University of Utah School of Medicine, Salt Lake City, Utah, USA
Manuscript received December 9, 1998;
revised manuscript received March 19, 1999,
accepted April 23, 1999.
Reprint requests and correspondence: Dr. Matthew A. Movsesian, Cardiology Division, 4A-100 SOM, University of Utah Health Sciences Center, 50 North Medical Drive, Salt Lake City, Utah 84132, USA
matthew.movsesian{at}hsc.utah.edu
Clinical trials of beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors in heart failure have demonstrated a reduction in survival in treated patients despite initial inotropic responses. These findings have led many to infer that activation of the mechanisms through which contractility is increased has deleterious effects on failing myocardium. It should be remembered, however, that these agents act proximately by raising intracellular cyclic adenosine monophosphate (cAMP) content and stimulating protein phosphorylation by cAMP-dependent protein kinase, and that the proteins whose phosphorylation contributes to the inotropic responses may be different from the proteins whose phosphorylation contributes to the reduction in survival. Evidence in support of the latter interpretation is presented, and potential therapeutic approaches through which the phosphorylation of different proteins might be selectively affected are considered.
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Abbreviations and Acronyms
| | cAMP | = cyclic adenosine monophosphate | | CREB | = cAMP-response element-binding protein |
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