In the present study in dogs, we compared with
aminophylline the
spasmolytic 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 induced with
serotonin: 10 microg/kg + 1 mg x kg(-1) x 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 microg/kg) 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 or
aminophylline. We then determined whether
propranolol (0.4 mg/kg) reversed the relaxation induced by
olprinone (1000 microg/kg, n = 6) or
aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each).
Olprinone and
aminophylline dose-dependently attenuated both PH and bronchoconstriction (
olprinone >
aminophylline: -logED(50)[mean] for PH and bronchoconstriction 5.37+/- 0.35[4.24 microg/kg] vs. 1.60+/-0.23[25.4 mg/kg] and 4.06+/-0.12[87.8 microg/kg] vs. 1.51+/-0.21[30.6 mg/kg], respectively). In addition,
olprinone produced more potent pulmonary vasodilation than bronchodilation while
aminophylline was equipotent. In addition, there was a significant increase in plasma
catecholamines after
olprinone (> or =100 microg/kg) and
aminophylline (> or =10 mg/kg). With the exception of
aminophylline-induced bronchodilation,
propranolol did not reverse any of the other effects measured. Therefore, the
spasmolytic effects of
olprinone are independent of plasma
catecholamines, while the bronchodilating effect of
aminophylline may partially involve increased levels of circulating
catecholamines.