Protective Effect of Various Antagonists of Inflammatory Mediators against Paraoxon-Induced Pulmonary Edema in the Rabbit

The protective effect of some antagonists of various inflammatory mediators against paraoxon-induced increases in endothelial permeability has been investigated in isolated perfused rabbit lungs. The edema induced by paraoxon has been previously related to a chain reaction mediated by acetylcholine. Lungs were ventilated and blood-free perfused with a constant flow. Arterial and venous pressures and lung weight were continuously recorded. Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). Paraoxon (4 x 10(-4) M) was injected in the perfusion circuit, in lungs with or without pretreatment with atropine, ketanserin, clonidine, morphine, indomethacin, and terfenadine plus cimetidine. Paraoxon induced a time-dependent increase in the Kf,c, a maximal effect being recorded 60 min after the injection. All the antagonists used as pretreatment significantly reduced the maximal effect recorded after paraoxon. These results show that muscarinic receptor antagonists, inhibitors of neuropeptides release, cyclooxygenase inhibitors, and 5-hydroxytryptamine and histamine receptor antagonists can protect the lung against the edema induced by paraoxon. This protective effect is due to inhibition of the chain reaction triggered by acetylcholine.