 Furthermore, PDE2 has been indicated to play a role in inflammatory responses as it has been detected in microvessels, but not in larger vessels.It has been speculated that tumor necrosis factor-alpha (TNFα) might regulate the function of PDE2 in endothelial cells and thereby affecting flow of fluid and cells through the endothelial barrier as in vitro experiments on endothelial cells show up regulation of both PDE2 mRNA and activity.Until now PDE2 inhibitors have mostly been used as research tools, but are presently being investigated for improving memory, for decreasing endothelial permeability under inflammatory conditions, and for preventing/improving heart failure and cardiac hypertrophy.The first specific inhibitor developed for PDE2 was EHNA ("erythro"-9-(2-hydroxy-3-nonyl)adenine).