Cyclic GMP (cGMP) made in response to atrial natriuretic peptide (ANP) or nitric oxide (NO)
http://circres.ahajournals.org/content/93/4/280
"The calcium surge associated with vasoconstrictor initiated contraction also activates a calcium/calmodulin-dependent PDE (PDE1A). Together, PDE5 and PDE1A lower cGMP sufficiently to allow contraction."
"Longer term, both PDE5 and PDE1A mRNA are induced by chronic stimulation of guanylyl cyclase. This induction is a major cause of the tolerance that develops to NO-releasing drugs."
"Under basal conditions (ie, low calcium levels), it is thought that the most active cGMP hydrolyzing PDE in smooth muscle is the cGMP-specific, cGMP-binding PDE, PDE5. Under higher calcium conditions (eg, during muscle contraction and possibly in cells being stimulated to divide), one or more of the PDE1 variants can become the predominant PDE."
"Tadalafil, a newer PDE5 inhibitor, has been reported as much more specific for PDE5 than for PDE6, but it is a relatively good inhibitor of PDE11, with an IC50 of 37 nmol/L. One of the newest PDE5 selective inhibitors, vardenafil, has an IC50 for PDE11 inhibition of 162 nmol/L. Sildenafil inhibits PDE11 with an IC50 of 2730 nmol/L.17"