TNF-α increases PDE2 activity but not PDE3 or PDE4 activities. Isoenzyme-specific cAMP-PDE activity for PDE2, PDE3, and PDE4 (A) and cGMP-PDE activity for PDE1, PDE2, and PDE5 (B) were measured for control (□) and TNF-α–stimulated (▪) HUVECs. Cells were stimulated for 18 hours with 10 ng/mL TNF-α. PDE activity was normalized to total cellular protein and expressed as pmol cAMP (or cGMP) × minute^-1 × mg protein^-1. PDE2 activity for cAMP increased 19-fold in the presence of TNF-α, whereas activity of PDE3 and PDE4 did not change (A). Increase in total cAMP PDE activity of TNF-α–stimulated cells is almost entirely attributable to the rise in PDE2 activity. Other cAMP PDE activities distinct from PDE2, 3, or 4 were detected at very low levels. Using cGMP as substrate, PDE2 was identified as the only significant PDE activity in HUVECs (B). TNF-α stimulation (10 ng/mL) increased PDE2 and hence total cGMP activity more than 8-fold. Data presented are mean ± SEM of 4 independent experiments. ^**P < .01 versus untreated cells.