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Review
. 2011 Dec;11(6):707-13.
doi: 10.1016/j.coph.2011.09.001. Epub 2011 Sep 28.

PDE3 inhibition in dilated cardiomyopathy

Matthew Movsesian  1 , Omar Wever-Pinzon, Fabrice Vandeput
Affiliations
Review

PDE3 inhibition in dilated cardiomyopathy

Matthew Movsesian et al. Curr Opin Pharmacol. 2011 Dec.

Abstract

In dilated cardiomyopathy, a condition characterized by chamber enlargement and reduced myocardial contractility, decreases in β-adrenergic receptor density and increases in Gαi and β-adrenergic receptor kinase activities attenuate the stimulation of adenylyl cyclase in response to catecholamines. PDE3 inhibitors have been used to 'overcome' the reduction in cAMP generation by blocking cAMP hydrolysis. These drugs increase contractility in the short-term, but long-term administration leads to an increase in mortality that correlates with an increase in sudden cardiac death. Whether separate mechanisms account for these beneficial and harmful effects, and, if so, whether PDE3 can be targeted so as to increase contractility without increasing mortality are questions that remain unanswered.

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Figures

Figure 1
Figure 1
Effects of phosphodiesterase (specifically, PDE3) inhibition on cAMP content in cardiac myocytes.
Figure 2
Figure 2
Generation of PDE3A isoforms in human cardiac myocytes.
Figure 3
Figure 3
Mechanisms of inotropic actions and adverse consequences of increasing intracellular cAMP content in failing myocardium.
See this image and copyright information in PMC

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