Role of leukotrienes during oleic acid-induced lung injury in pigs.
We hypothesized that leukotrienes might contribute to the pathophysiology of acute lung injury induced by oleic acid. Oleic acid (2-20 mg.kg-1.h-1), LY171883 [leukotriene (LT) D4/LTE4 receptor antagonist, 10 mg/kg + 1 mg.kg-1.h-1] + oleic acid (10 mg.kg-1. h-1), or triolein (20 mg.kg-1.h-1) were infused intravenously into anesthetized pigs. Treatment with the cyclooxygenase inhibitor was designed to possibly enhance LT release. Bronchoalveolar lavage fluid concentrations of LTB4, LTC4, LTD4, and LTE4 were measured by reverse-phase high-performance liquid chromatography and radioimmunoassay. Oleic acid caused dose-related hypoxemia and pulmonary hypertension and increased pulmonary vascular resistance, lung water, and alveolar-capillary membrane permeability. Bronchoalveolar lavage fluid levels of LTB4, LTC4, LTD4, and LTE4 showed no significant changes in oleic acid- or indomethacin + oleic acid-treated pigs, compared with triolein-treated controls. Indomethacin modestly attenuated the oleic acid-induced hypoxemia and the early increases (i.e., 0-0.5 h) in mean pulmonary arterial pressure and pulmonary vascular resistance. In contrast, LY171883 provided no protection against any oleic acid-induced cardiopulmonary effect (measured or calculated). We conclude that LTs are not likely to be important mediators of oleic acid-induced lung injury in the pig.
Kruse-Elliott
K
K
Department of Anatomy, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Olson
N C
NC
D000098:Acetophenones / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D012898:Autacoids / Q000037:antagonists & inhibitors; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D017999:Leukotriene E4; D015289:Leukotrienes / Q000502:physiology*; D008168:Lung / Q000098:blood supply; D019301:Oleic Acid; D009829:Oleic Acids; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000503:physiopathology*; D013189:SRS-A / Q000031:analogs & derivatives / Q000378:metabolism; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology; D014304:Triolein / Q000494:pharmacology; D014655:Vascular Resistance
D000098:Acetophenones; D012898:Autacoids; D015289:Leukotrienes; D009829:Oleic Acids; D013189:SRS-A; D013777:Tetrazoles; D014304:Triolein; D007975:Leukotriene B4; D019301:Oleic Acid; D017999:Leukotriene E4; C044660:LY 171883; D007213:Indomethacin