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 medi ators against paraoxon-induced increases in endothelial permeability h as been investigated in isolated perfused rabbit lungs. The edema indu ced by paraoxon has been previously related to a chain reaction mediat ed by acetylcholine. Lungs were ventilated and blood-free perfused wit h a constant flow. Arterial and venous pressures and lung weight were continuously recorded. Endothelial permeability was evaluated by measu ring the capillary filtration coefficient (K-f,K-c). Paraoxon (4 X 10( -4) M) was injected in the perfusion circuit, in lungs with or without pretreatment with atropine, ketanserin, clonidine, morphine, indometh acin, and terfenadine plus cimetidine. Paraoxon induced a time-depende nt increase in the K-f,K-c, a maximal effect being recorded 60 min aft er the injection. All the antagonists used as pretreatment significant ly reduced the maximal effect recorded after paraoxon. These results s how that muscarinic receptor antagonists, inhibitors of neuropeptides release, cyclooxygenase inhibitors, and 5-hydroxytryptamine and histam ine receptor antagonists can protect the lung against the edema induce d by paraoxon. This protective effect is due to inhibition of the chai n reaction triggered by acetylcholine. (C) 1995 Academic Press, Inc.