Nonadrenergic effects of isoproterenol in dogs with hypoxic pulmonary vasoconstriction. Possible role of prostaglandins.
To determine whether the pulmonary vasodilation produced by isoproterenol is mediated solely by its beta adrenergic effects, we studied the hemodynamic responses to isoproterenol in three groups of dogs with pulmonary vasoconstriction produced by continuous ventilation with 10% oxygen: (a) hypoxia alone, (b) hypoxia and propranolol 0.3 mg/kg i.v. bolus followed by an infusion of 5 micrograms/kg per min, and (c) hypoxia after pretreatment with an inhibitor of cyclooxygenase, either indomethacin or meclofenamate 5 mg/kg s.c. twice daily for 2 d prior to study. All groups had similar values for mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance (PVR) during room air and hypoxic ventilation. Isoproterenol in doses of 0.0025, 0.005, and 0.05 micrograms/kg per min produced a dose-related decline in PAPm and PVR during hypoxia in group 1. Despite beta-blockade with propranolol (group 2), isoproterenol at all three doses significantly reduced PAPm and PVR. The responses to isoproterenol were comparable in the presence or absence of propranolol; at 0.05 micrograms/kg per min the effects of isoproterenol were blunted, but not abolished, by propranolol. Similar results were observed even when five times the dose of propranolol was given. Isoproterenol at all three doses had no effect, however, on PAPm and PVR in the cyclooxygenase inhibitor-pretreated group. These data suggest that the pulmonary vasodilator effects of isoproterenol are not mediated solely by pulmonary vascular beta adrenergic receptors, and that vasodilator prostaglandins may play a role in the responses to this drug.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011433:Propranolol; D007545:Isoproterenol