Cyclooxygenase inhibitors prevent ethchlorvynol-induced injury in rat and rabbit lungs.
The effect of three chemically dissimilar cyclooxygenase inhibitors on ethchlorvynol-(ECV) induced acute lung injury was studied in isolated buffer-perfused rat and blood-perfused rabbit lungs. ECV caused the microvascular fluid filtration coefficient (Kf) to increase by greater than threefold in the rat lungs and twofold in the rabbit lungs. ECV caused increased pulmonary vascular resistance (PVR) and microvascular pressure measured by the double occlusion technique (Pdo) compared with the vehicle control group in the rat experiments. However, ECV had no effect on PVR or Pdo in the rabbit experiments. Pretreatment with the cyclooxygenase inhibitors indomethacin, ibuprofen, and meclofenamate prevented the increase in microvascular permeability in both the rat and rabbit lung preparations. The cyclooxygenase inhibitors also prevented the ECV-induced PVR and Pdo increases in the rat lungs but had no effect on PVR or Pdo in the rabbit lungs. These results indicate that cyclooxygenase products of arachidonate metabolism mediate the ECV-induced Kf increase in both isolated rat and rabbit lungs.
Department of Pharmacology, St Louis University School of Medicine, Missouri 63110.
P B
PB
Zanaboni
J D
JD
Bradley
R O
RO
Webster
T E
TE
Dahms
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004984:Ethchlorvynol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008171:Lung Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D008469:Meclofenamic Acid; D004984:Ethchlorvynol; D007052:Ibuprofen; D007213:Indomethacin