A long-acting prostacyclin agonist with thromboxane inhibitory activity for pulmonary hypertension

Rationale: The balance between prostacyclin and thromboxane plays an important role in the regulation of pulmonary vascular tone. Recently, we developed ONO-1301, a novel, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity.Objectives: We investigated whether modulation of prostacyclin/thromboxane balance by ONO-1301 ameliorates monocrotaline-induced pulmonary hypertension in rats.Methods: After subcutaneous injection of monocrotaline or vehicle, rats were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle twice per day for 3 wk.Measurements and Main Results: There was significant development of pulmonary hypertension 3 wk after monocrotaline injection. Treatment with ONO-1301 significantly attenuated the increases in right ventricular systolic pressure and ratio of right ventricular weight to body weight in monocrotaline rats. Furthermore, ONO-1301 significantly attenuated the increase in medial wall thickness of peripheral pulmonary arteries in m...