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(Hypertension. 2003;41:e2.)
© 2003 American Heart Association, Inc.

Letters to the Editor

Does Sildenafil Indirectly Inhibit Phosphodiesterase 3 in Vascular Smooth Muscle?

Career Investigator, Heart and Stroke Foundation of Ontario, Associate Professor of Pharmacology and Toxicology, Queen’s University, Kingston, Ontario, Canada, E-mail mauriced@post.queensu.ca

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

I read with great interest the recent report by Schalcher et al, entitled "Interaction of Sildenafil With cAMP-Mediated Vasodilation In Vivo."¹ The data presented deals with a potentially important issue and, given the increasing interest in using phosphodiesterase 5 (PDE5) inhibitors for various conditions, in addition to erectile dysfunction, are also timely. As a researcher studying the role of cyclic nucleotide phosphodiesterases (PDEs) in cardiovascular tissues, I would like to take this opportunity to comment on some of the statements made in the discussion of these data. First, since a considerable literature describing the importance of interactions between cGMP and cAMP hydrolyzing PDEs has accumulated in recent years, the finding that sildenafil and cAMP-dependent vasodilators interacted to regulate forearm blood flow (FBF) in this study should, perhaps, not have been described as "unexpected."² In earlier work, Dr Richard Haslam and I reported that cGMP elevating agents (for example nitroprusside) increased cAMP through a cGMP-dependent inhibition of the cAMP-hydrolyzing phosphodiesterase 3 (PDE3) in blood platelets and arterial smooth muscle.^3–5 This effect of cGMP on cAMP hydrolysis in these cells allowed a marked synergistic increase in platelet or smooth muscle cAMP when activators of adenylyl cyclase and guanylyl cyclase were used together, as well as a cAMP-dependent synergistic inhibition of blood platelet aggregation and arterial smooth muscle contraction. More recently, similar reports have described this effect in cardiac myocytes and mesangial cells,^6,7 perhaps indicating that interactions between cGMP and cAMP are important in several cell types and challenging the concept that the . . . [Full Text of this Article]