title: Endotoxaemia in rats: role of NO, PAF and TXA2 in pulmonary neutrophil sequestration and hyperlactataemia.
abstract: OBJECTIVE
  The involvement of PAF, TXA2 and NO in LPS-induced pulmonary neutrophil sequestration an hyperlactataemia was studied in conscious rats. As pharmacological tools WEB 2170 (PAF receptor antagonist, 20 mg/kg), camongarel (inhibitor of TXA2 synthase, 30 mg/kg), N(G)-nitro L-arginine methyl ester (L-NAME -- non-selective nitric oxide synthase inhibitor, 30 mg/kg) were used.
  
  
  METHODS
  Plasma lactate and NO2-/NO3- levels as well as myeloperoxidase (MPO) activity in lung tissue were measured one and five hours after administration of LPS (4 mg/kg(-1)).
  
  
  RESULTS
  LPS induced a twofold increase in plasma lactate levels and nearly 10-fold increase in plasma NO2-/NO3- levels five but not one hour after LPS administration. However, LPS-induced increase in pulmonary MPO activity was seen at both time intervals. Neither WEB 2170 nor camonagrel changed one or five hours responses to LPS (lactate, NO2-/NO3-, MPO). L-NAME potentiated LPS-induced rise in MPO activity in the lung and this potentiation was not affected by WEB 2170 or camonagrel. L-NAME supressed plasma NO2-/NO3- response and substantially potentiated plasma lactate response to LPS and both effects were partially reversed by WEB 2170 or camonagrel.
  
  
  CONCLUSIONS
  In summary, we demonstrated that PAF and TXA 2 play a role in overproduction of lactate during endotoxaemia in NO-deficient rats. However, these lipids do not mediate endotoxin-induced sequestration of neutrophils in the lung.
authors.affiliation: Jagiellonian University College of Medicine, Department of Pharmacology, Cracow, Poland. mfolszan@cyf-kr.edu.pl
authors.forename: R
authors.initials: R
authors.lastname: Olszanecki
authors.forename: S
authors.initials: S
authors.lastname: Chłopicki
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002465:Cell Movement; D019446:Endotoxemia / Q000378:metabolism* / Q000473:pathology; D007189:Indans / Q000494:pharmacology; D019344:Lactic Acid / Q000096:biosynthesis / Q000097:blood*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000473:pathology*; D009569:Nitric Oxide / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013928:Thromboxane A2 / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D007189:Indans; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; D009569:Nitric Oxide; D019344:Lactic Acid; D013928:Thromboxane A2; C063964:bepafant; D019331:NG-Nitroarginine Methyl Ester; C103583:camonagrel