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Beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors: Shifting the focus from inotropy to cyclic adenosine monophosphate



Beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors: Shifting the focus from inotropy to cyclic adenosine monophosphate



Journal of the American College of Cardiology 34(2): 318-324



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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Accession: 010234731

Download citation: RISBibTeXText

PMID: 10440139

DOI: 10.1016/s0735-1097(99)00220-x


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