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Cardiovascular implications in the use of PDE5 inhibitor therapy


Cardiovascular smooth muscle cells (SMCs) exist as resting or activated cells. Resting SMCs produce contractile proteins and are nearly transcriptionally inactive; activated SMCs are transcriptionally active and are involved in pathological processes such as atherosclerosis. Soluble guanylate cyclase, protein kinase G, and protein kinase A are present in SMCs, but their levels can be decreased in activated cells. Phosphodiesterase 3 (PDE3) activity is abundant in cardiovascular tissues; both PDE3A and PDE3B are involved in cyclic adenosine monophosphate (cAMP) hydrolysis in these tissues. Cyclic-AMP-hydrolyzing PDE activities are altered during the phenotypic transition of SMCs from the resting to the activated phenotype. Similar changes have been observed in cyclic guanosine monophosphate cGMP-hydrolyzing PDEs, although the impact of these alterations on PDE5 inhibitor-mediated effects requires further study. This report presents the changes in PDE expression that accompany phenotypic modulation of SMCs and discusses the potential impact of these events on PDE5-mediated cell functions.

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Correspondence to D H Maurice.

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Maurice, D. Cardiovascular implications in the use of PDE5 inhibitor therapy. Int J Impot Res 16 (Suppl 1), S20–S23 (2004).

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  • phosphodiesterase
  • smooth muscle cells
  • cyclic AMP
  • cyclic GMP
  • protein kinase


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