Endotoxin-induced lung injury in rats: role of eicosanoids.
We studied lung vascular injury and quantitated lung eicosanoids in rats after intraperitoneal injection of Salmonella enteritidis endotoxin. Within 40 min after endotoxin injection (20 mg/kg), lung tissue thromboxane B2 doubled, although 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) increased by 8- to 10-fold. Lung 5-hydroxyeicosatetraenoic acid and leukotriene C4 were variably increased by endotoxin. The levels of all eicosanoids returned to base line 6 h after endotoxin challenge. Lung vascular injury, as assessed by the extravascular accumulation of 125I-albumin and water in isolated perfused lungs, was observed 90 min after endotoxin injection (0.02-20 mg/kg) in vivo. Inhibition of the cyclooxygenase pathway with indomethacin and the lipoxygenase pathway with diethylcarbamazine and 2-(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoqui none failed to attenuate endotoxin-induced lung injury. In addition, essential fatty acid deficiency, which markedly reduced lung tissue levels of 6-keto-PGF1 alpha, thromboxane B2, and leukotriene C4, did not protect against endotoxin injury. We conclude that although lung eicosanoids are activated during endotoxemia, they do not play a crucial role in the development of acute lung vascular injury in rats.
Chang
S W
SW
Pulmonary Division, University of Colorado Health Sciences Center, Denver 80262.
Westcott
J Y
JY
Pickett
W C
WC
Murphy
R C
RC
Voelkel
N F
NF
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D004049:Diethylcarbamazine / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D005227:Fatty Acids / Q000097:blood; D005228:Fatty Acids, Essential / Q000172:deficiency; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013189:SRS-A / Q000378:metabolism*; D012477:Salmonella enteritidis; D013929:Thromboxane B2 / Q000378:metabolism*
D004731:Endotoxins; D005227:Fatty Acids; D005228:Fatty Acids, Essential; D008070:Lipopolysaccharides; D013189:SRS-A; D000001:Calcimycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D004049:Diethylcarbamazine