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 weight (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 significantly reduced (p < 0.05) by ICP 198,615 (bolus 15 mg/kg, infusion 15 mg/kg/h). Thrombin infusion caused a significant increase in myeloperoxidase activity in the lung tissue (p < 0.05), This increase was further accentuated by ICI 198,615, indicating that the effect of this antagonist is not due to reduction of leukocyte infiltration in the lungs, The results thus show that a leukotriene receptor antagonist effectively counteracts the increase in lung vascular permeability to protein caused by thrombin, and indicate that leukotrienes are important mediators of thrombin-induced pulmonary edema in the rat.