Involvement of PAF-acether and eicosanoids in adrenaline-induced pulmonary edema in mice

The participation of platelet-activating factor (PAF, PAF-acether) in a mouse model of pulmonary edema was studied using specific antagonists. Mice were treated before induction of edema with the PAF antagonists BN52021 (10 mg/kg, ip), PCA4248 (10 mg/kg, po) or WEB2170 (10 mg/kg, ip), the lipoxygenase inhibitor EP10161 (10 mg/kg, ip), the cyclo-oxygenase inhibitor aspirin (250 mg/kg, po), or with the mixed cyclo-lipoxygenase inhibitor BW755C (50 mg/kg, ip). The test drugs were administered to animals either 30 min (when the ip route was used) or 60 min (when given po) prior to the induction of pulmonary edema. Pulmonary edema was induced by intravenous administration of adrenaline (2 mg/kg). When the lung-body index was used as the criterion for comparison between groups, BN52021, PCA4248 and WEB2170 were found to have no significant effect on pulmonary edema. In contrast, EP10161, aspirin and BW755C significantly inhibited pulmonary edema by 49%, 30% and 27%, respectively. The results suggest that arachidonate metabolites are likely to play a major role in adrenaline-induced pulmonary edema in mice, whereas PAF-acether does not seem to play an important role in this model.