Cardiovascular implications in the use of PDE5 inhibitor therapy

International Journal of Impotence Research
Donald H Maurice

Abstract

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.

References

Dec 4, 1990·European Journal of Pharmacology·D H Maurice, R J Haslam
Nov 28, 2001·The Journal of Biological Chemistry·Sergei D RybalkinJoseph A Beavo
Jul 11, 2002·American Journal of Physiology. Cell Physiology·Asa B Gustafsson, Laurence L Brunton

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Citations

Jun 2, 2006·Critical Reviews in Toxicology·Charles M Yarborough
Sep 20, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·K A MorrowT Stevens

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