ROLE OF EICOSANOIDS IN PAF-INDUCED INCREASES OF THE VASCULAR-PERMEABILITY IN RAT AIRWAYS

1. Platelet activating factor (PAF; 1.0 and 5.0 μg kg-1) injected in the tail vein of unanaesthetized rats dose-dependently increased the vascular permeability of the trachea, upper and lower bronchi (up to 400%) as measured by the extravasation of Evans blue dye. The permeability of the parenchyma was not affected by PAF treatment. 2. Pretreatment of the animals with an intravenous injection of the PAF antagonist BN-52021 (10 mg kg-1) abolished almost totally the vascular permeability changes elicited by PAF injection (5.0 μg kg-1). 3. Pretreatment of the animals with intravenous injections of inhibitors of thromboxane formation, indomethacin (10 mg kg-1) and compound OKY-046 (10 mg kg-1), and thromboxane antagonist, compound L-655,240 (5 mg kg-1), partially reduced PAF effects in the airways (from 28 to 69%). The thromboxane mimic U-44069 (5 μg kg-1) did not modify the vascular permeability of rat airways. The effect of a low dose of PAF (0.1 μg kg-1) on the vascular permeability of the trachea and bronchi (but not of the parenchyma) was potentiated by compound U-44069 (5.0 μg kg-1) or noradrenaline (400 ng kg-1) whereas the effect of a high dose of PAF (5.0 μg kg-1) was not affected. 4. Neither the peptidoleukotriene antagonist MK-571 (10 mg kg-1) nor the 5-lipoxygenase inhibitor, L-663,536 (10 mg kg-1) given before the injection of PAF (5.0 μg kg-1) affected the protein extravasation in rat lung tissues. 5. These data suggest that the effect of PAF on rat vascular permeability is partly modulated by thromboxane formation although thromboxanes have no direct effect on the permeability. Thromboxane may act via a vasoconstriction that increases hydrostatic pressure and potentiates the extravasation elicited by PAF effect on endothelial cells. 6. Leukotrienes do not appear to be involved in the changes of rat airway permeability induced by PAF.