Treatment of pulmonary hypertension has not yet been established and effective drug therapies are required. We hypothesized that inhibition of cyclic guanosine monophoshate (cGMP)- phosphodiesterase (PDE) would result in specific vasodilation of the hypertensive pulmonary arteries. This study was carried out to determine whether PDE V inhibitors could dilate pulmonary artery (PA) from monocrotaline-induced pulmonary hypertensive rats. Thirty-six Wistar rats were given either monocrotaline (105 mg/kg) or normal saline (control) subcutaneously. Three weeks later, the PA rings were isolated and mounted in 5-mL organ chambers. After precontraction with norepinephrine (0.1 μmM), one of two PDE V inhibitors, zaprinast and dipyridamole, was added in a cumulative fashion. We also investigated whether nitric oxide synthetase (NOS) inhibitor modifies the effects of the PDE V inhibitors on the PA. Zaprinast and dipyridamole dose-dependently dilated the PA from either saline- or monocrotaline- treated rats. There was no difference in the dilatory effect between monocrotaline and saline rats. Pretreatment of a NOS inhibitor (N^G-nitro-L-arginine methyl ester (0.1 mM)) reduced moderately the vasodilatory effect of zaprinast on the PA from monocrotaline-treated but not saline-treated rats. The results suggest that PDE V inhibitors exert a strong vasodilating effect on PA of pulmonary hypertensive rats as well as on that of normal rats, and that NO plays a role, at least in part, in the effect of PDE V inhibition on PA of pulmonary hypertensive rats.