Effect of lipoxygenase and cyclo-oxygenase inhibition on oleic acid-induced lung oedema.
The contribution of cyclo-oxygenase and 5-lipoxygenase metabolites on hemodynamics and oedema formation was investigated in 21 isolated rabbit lungs after a 10 min Oleic Acid (OA) infusion, by recording the changes on Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP). Lungs (n = 7) were pre-treated with indomethacin (cyclo-oxygenase inhibitor) 50 min prior to OA or with Diethylcarbamazine (5-lipoxygenase inhibitor) (n = 7) or not pre-treated at all (control group, n = 7). The FFR in the indomethacin group was significantly greater than in the control and Diethylcarbamazine (DEC) groups 12 min after OA (7.6 +/- 2.3 mg.min-1 vs. 2.3 +/- 0.8 mg.min-1 and 0.96 +/- 0.8 mg.min-1 respectively) (P < 0.01). The FFR in the control lungs 20 min after OA was significantly greater than the corresponding DEC value (4.2 +/- 0.5 mg.min-1 vs. 1.6 +/- 1.0 mg.min-1) (P < 0.01). Mean Pulmonary Artery Pressure (MPAP) increased both in control and indomethacin groups (16.0 +/- 2.0 Torr to 24.3 +/- 3.7 Torr after 20 min OA and 14.4 +/- 2.5 Torr to 24.6 +/- 3.6 Torr at 10 min after OA, respectively), but MPAP value in DEC group did not significantly change 30 min after OA (14.7 +/- 1.5 Torr to 16.0 +/- 2.3 Torr) (P > 0.05). So we conclude that the selective inhibition of the 5-lipoxygenase metabolites (leukotriene-5hete) may play a protective role in OA induced oedema, whereas the selective inhibition of the cyclo-oxygenase pathway may have a deleterious effect on the hemodynamics and endothelial permeability in our experimental condition.
Angeli
S
S
Respiratory Physiology Unit, Medical Faculty, Universidad Central de Venezuela, Caracas.
Bonnet
A
A
Zabner
J
J
Martinez-Ruiz
R
R
Sánchez de León
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007260:Infusion Pumps; D016859:Lipoxygenase Inhibitors; D009829:Oleic Acids; D011292:Premedication; D011651:Pulmonary Artery / Q000502:physiology; D011654:Pulmonary Edema / Q000139:chemically induced*; D011817:Rabbits
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D009829:Oleic Acids; D007213:Indomethacin