A comparison of the spasmolytic effects of olprinone and aminophylline on serotonin-induced pulmonary hypertension and bronchoconstriction with or without beta-blockade in dogs

In the present study in dogs, we compared with aminophylline the spasmolyti c effects of olprinone, a novel phosphodiesterase 3 inhibitor, on serotonin -induced pulmonary hypertension (PH) and bronchoconstriction. Mongrel dogs were anesthetized with pentobarbital. PH and bronchoconstriction were induc ed with serotonin: 10 mug/kg + 1 mg.kg(-1).h(-1), and assessed as % changes in pulmonary vascular resistance and bronchial cross-sectional area (basal = 100%). Initially, the relaxant effects of olprinone (n = 8: 0-1000 mug/k g) and aminophylline (n = 8: 0-100 mg/kg) were compared. Pulmonary vascular resistance and bronchial cross-sectional area were assessed before and 30 min after serotonin infusion began and 5 min after each dose of olprinone o r aminophylline. We then determined whether propranolol (0.4 mg/kg) reverse d the relaxation induced by olprinone (1000 mug/kg, n = 6) or aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each). Olprinone and aminop hylline dose-dependently attenuated both PH and bronchoconstriction (olprin one > aminophylline: -logED(50)[mean] for PH and bronchoconstriction 5.37 /- 0.35[4.24 mug/kg] vs 1.60 +/- 0.23[25.4 mg/kg] and 4.06 +/- 0.12[87.8 mu g/kg] vs 1.51 +/- 0.21[30.6 mg/kg], respectively). In addition, olprinone p roduced more potent pulmonary vasodilation than bronchodilation while amino phylline was equipotent. In addition, there was a significant increase in p lasma catecholamines after olprinone (greater than or equal to 100 mug/kg) and aminophylline (>10 mg/kg). With the exception of aminophylline-induced bronchodilation, propranolol did not reverse any of the other effects measu red. Therefore, the spasmolytic effects of olprinone are independent of pla sma catecholamines, while the bronchodilating effect of aminophylline may p artially involve increased levels of circulating catecholamines.