We examined the influence of K+ channel antagonists on the vasorelaxation induced by theophylline (non selective PDEI), siguazodan (PDE3I), rolipram (PDE4I) and zaprinast (PDE5I) in human intralobar pulmonary arteries. All PDEI tested induced a concentration-dependent relaxation with theophylline being significantly (p < 0.05) more efficient and rolipram more potent than PDE5I and PDE3I (Emax values, expressed as a percentage of maximal relaxation by papaverine 10(-4)M, were 92% +/- 2%, 84% +/- 8%, 90% +/- 4% and 99% +/- 1%, and pD2 values were 7.30 +/- 0.35, 6.14 +/- 0.25, 5.86 +/- 0.17, and 4.85 +/- 0.47 for rolipram, siguazodan, zaprinast and theophylline, respectively). 4-Aminopyridine (4-AP, Kv, voltage dependent channel blocker, 1 mM) induced a significant increase (+17% p < 0.05) of U46619-induced vasoconstriction whereas the other K+-channels blockers, glibenclamide (KATP channels, 1 microM) charybdotoxin (predominant BKCa, large conductance Ca2+-sensitive K+ channels, 0.1 microM) and apamine (SKCa, small conductance, 0.3 microM) were without effect. The concentration response curves (CRC) for rolipram were significantly shifted to the right by glibenclamide (1 microM), charybdotoxin (0.1 microM) and 4-AP (1 mM). The CRC for siguazodan was significantly displaced to the right by 4-AP. None of the potassium channel blockers displaced the CRC for zaprinast and theophylline. Apamine was without effect on the CRC for all the PDEI used in this study. (1) PDE3, 4 and 5 are functionally present in human intralobar pulmonary arteries; (2) the vasoconstriction induced by U46619 is downregulated by 4-aminopyridine sensitive-K+ channels; (3) the relaxant effects of rolipram (PDE4I) are partly mediated through KATP, BKCa, and Kv potassium channels and those of siguazodan (PDE3I) by Kv potassium channels.