BENEFICIAL-EFFECTS OF A LEUKOTRIENE RECEPTOR ANTAGONIST ON THROMBIN-INDUCED PULMONARY-EDEMA IN THE RAT

The effect of a selective leukotriene receptor antagonist, the peptide ICI 198,615, on thrombin-induced pulmonary edema was studied in rats, Administration of thrombin produced a significant increase in lung we ight (p < 0.05), wet weight to dry weight ratio (WW/DW; p < 0.05), and relative lung water content (p < 0.05). These increases were all sign ificantly reduced (p < 0.05) by ICP 198,615 (bolus 15 mg/kg, infusion 15 mg/kg/h). Thrombin infusion caused a significant increase in myelop eroxidase activity in the lung tissue (p < 0.05), This increase was fu rther accentuated by ICI 198,615, indicating that the effect of this a ntagonist is not due to reduction of leukocyte infiltration in the lun gs, The results thus show that a leukotriene receptor antagonist effec tively counteracts the increase in lung vascular permeability to prote in caused by thrombin, and indicate that leukotrienes are important me diators of thrombin-induced pulmonary edema in the rat.