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.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 8 print issues and online access
$259.00 per year
only $32.38 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Liu H, Maurice DH . Expression of cyclic GMP-inhibited phosphodiesterases 3A and 3B (PDE3A and PDE3B) in rat tissues: differential subcellular localization and regulated expression by cyclic AMP. Br J Pharmacol 1998; 125: 1501–1510.
Palmer D, Maurice DH . Dual expression and differential regulation of phosphodiesterase 3A and phosphodiesterase 3B in human vascular smooth muscle: implications for phosphodiesterase 3 inhibition in human cardiovascular tissues. Mol Pharmacol 2000; 58: 247–252.
Dunkerley HA et al. Reduced phosphodiesterase 3 activity and phosphodiesterase 3A level in synthetic vascular smooth muscle cells: implications for use of phosphodiesterase 3 inhibitors in cardiovascular tissues. Mol Pharmacol 2002; 61: 1033–1040.
Maurice DH, Haslam RJ . Molecular basis of the synergistic inhibition of platelet function by nitrovasodilators and activators of adenylate cyclase: inhibition of cyclic AMP breakdown by cyclic GMP. Mol Pharmacol 1990; 37: 671–681.
Maurice DH, Haslam RJ . Nitroprusside enhances isoprenaline-induced increases in cAMP in rat aortic smooth muscle. Eur J Pharmacol 1990; 191: 471–475.
Rybalkin SD et al. Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype. J Clin Invest 1997; 100: 2611–2621.
Rybalkin SD et al. Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem 2002; 277: 3310–3317.
Tilley DG, Maurice DH . Vascular smooth muscle cell phosphodiesterase (PDE) 3 and PDE4 activities and levels are regulated by cyclic AMP in vivo. Mol Pharmacol 2002; 62: 497–506.
Kim D et al. Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation 2001; 104: 2338–2343.
Dickinson NT, Jang EK, Haslam RJ . Activation of cGMP-stimulated phosphodiesterase by nitroprusside limits cAMP accumulation in human platelets: effects on platelet aggregation. Biochem J 1997; 323: 371–377.
Gustafsson AB, Brunton LL . Attenuation of cAMP accumulation in adult rat cardiac fibroblasts by IL-1beta and NO: role of cGMP-stimulated PDE2. Am J Physiol Cell Physiol 2002; 283: C463–C471.
Lugnier C, Keravis T, Eckly-Michel A . Cross talk between NO and cyclic nucleotide phosphodiesterases in the modulation of signal transduction in blood vessel. J Physiol Pharmacol 1999; 50: 639–652.
Rights and permissions
About this article
Cite this article
Maurice, D. Cardiovascular implications in the use of PDE5 inhibitor therapy. Int J Impot Res 16 (Suppl 1), S20–S23 (2004). https://doi.org/10.1038/sj.ijir.3901210
- smooth muscle cells
- cyclic AMP
- cyclic GMP
- protein kinase