The effect of the prostaglandin I2 analogue OP-2507 on adrenaline-induced pulmonary edema in rabbits and analysis of hemodynamic changes

Jpn J Pharmacol. 2000 Jun;83(2):125-34. doi: 10.1254/jjp.83.125.

Abstract

This study was carried out to understand the onset mechanism of adrenaline (ADR)-induced pulmonary edema (PE) and the effect of drugs related to the arachidonate cascade in a rabbit model. ADR was administered intravenously by a bolus injection to the rabbits at 50, 75 and 100 microg/kg. To evaluate the severity of PE, the lung-water ratio (LWR) was calculated as a ratio of the difference between wet and dry lung weight to dry lung weight. The PE incidence and LWR exhibited a dose-dependent increase, and LWR correlated with the left atrial pressure (LAP). The involvement of the arachidonate cascade was evaluated by the co-administration of flurbiprofen, a cyclooxygenase inhibitor; ozagrel, a thromboxane synthase inhibitor; and OP-2507 (15-cis-(4-n-propylcyclohexyl)-6,17,18, 19,20-pentanor-9-deoxy-6,9-alpha-nitriloprostaglandin F1 methyl ester), a prostaglandin I2 analogue. Co-treatment of the rabbits with ADR and flurbiprofen resulted in an increase in LAP and the incidence of PE, whereas co-administration of ozagrel did not exhibit any significant changes in the measured parameters. Conversely, OP-2507 reduced the LAP, PE incidence and LWR when co-administered with ADR. Rabbits co-treated with OP-2507 displayed an improved cardiac function. The results of these studies demonstrated the effectiveness of OP-2507 in protecting the lung and cardiac function from the ADR-induced PE.

MeSH terms

  • Animals
  • Cyclooxygenase Inhibitors / pharmacology
  • Epinephrine / adverse effects*
  • Epinephrine / blood
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacology
  • Flurbiprofen / pharmacology
  • Methacrylates / pharmacology
  • Models, Animal
  • Pulmonary Edema / chemically induced*
  • Pulmonary Edema / physiopathology*
  • Rabbits
  • Thromboxane-A Synthase / antagonists & inhibitors

Substances

  • Cyclooxygenase Inhibitors
  • Methacrylates
  • Flurbiprofen
  • OP 2507
  • Epoprostenol
  • Thromboxane-A Synthase
  • ozagrel
  • Epinephrine