Oleic acid-induced pulmonary injury in rats: potential role of sulfidopeptide leukotrienes.
Lung injury following intravenous oleic acid is characterized by pulmonary edema, leukopenia and hypoxemia. Because leukotrienes can increase permeability and cause leukocyte adherence, we evaluated their potential role in oleic acid-induced lung injury in the anesthetized rat using a selective LTD4/E4 antagonist, LY171883. 99mTc-albumin and 99mTc-red blood cells (99mTc-RBC) were used to measure changes in the pulmonary permeability index and intravascular space by non-invasive scintigraphy. Intravenous oleic acid (0.06 ml/kg) increased the pulmonary permeability index 11 (P less than 0.01) and 5.8 fold (P less than 0.01) at 5 and 50 min after its injection compared to baseline, but had no effect on mean pulmonary arterial pressure or pulmonary distribution of 99mTc-RBC. Oleic acid also induced arterial hypoxemia, and increased bronchoalveolar lavage-fluid levels of immunoreactive (i) leukotriene LTC4 from 0.40 +/- 0.14 ng/ml to 2.27 +/- 0.55 ng/ml (mean +/- S.E.M., n = 4, P less than 0.05) and iLTB4 (from 0.42 +/- 0.05 ng/ml to 1.91 +/- 0.63 ng/ml, n = 5-7, P less than 0.01). LY171883 attenuated the elevated permeability by 24% and 68% at 5 (P less than 0.05) and 50 min (P less than 0.01), but did not alter the hypoxemia. These results support the hypothesis that oleic acid elevates leukotriene levels which may increase pulmonary vascular permeability. Furthermore, they suggest that the prevention of elevated pulmonary vascular permeability and edema may be necessary, but are clearly not sufficient to prevent arterial hypoxemia following oleic acid injury in the rat.
Ball
H A
HA
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.
Cook
J A
JA
Spicer
K M
KM
Hsu
C Y
CY
Halushka
P V
PV
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004112:Dimercaprol / Q000378:metabolism; D007970:Leukopenia / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D017999:Leukotriene E4; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids; D010100:Oxygen / Q000097:blood; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D013189:SRS-A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D000098:Acetophenones; D009829:Oleic Acids; D013189:SRS-A; D013777:Tetrazoles; D004112:Dimercaprol; D007975:Leukotriene B4; D019301:Oleic Acid; D017999:Leukotriene E4; C044660:LY 171883; D010100:Oxygen