HN-10200, a nonselective inhibitor of phosphodiesterase, has positive inotropic and vasodilator activity. The present study was designed to determine the role of endotheliumin in causing relaxation to HN-10200 in isolated canine femoral and basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% 02, 6% CO2 (t = 37°C; pH = 7.4). HN-10200 and another nonselective phosphodiesterase inhibitor, 3-isobutyl-l-methyl-xanthine (IBMX), caused similar concentration-dependent relaxations in femoral arteries with and without endothelium. In femoral arteries without endothelium, HN-10200 and IBMX significantly augmented relaxations to prostacyclin, but did not affect relaxations to a nitric oxide donor 3-morpholinosydnonimine (SIN-l) or endothelium-derived relaxing factor (EDRF) released by bradykinin. In basilar arteries, relaxations to HN-10200 were augmented by the removal of endothelium, whereas relaxations to IBMX were not affected. Relaxations to prostacyclin, SIN-l, and EDRF were not affected by the presence of phosphodiesterase inhibitors. The results of the present study suggest that HN-10200 causes endotheliumindependent relaxations. In addition, it may augment relaxations to prostacyclin but does not affect relaxations to EDRF.