title: Alveolar endotoxin increases alveolar liquid clearance in rats.
abstract: Under some pathological conditions, ion transport across alveolar epithelial cells is downregulated, whereas under other pathological conditions, it may be upregulated. Because endotoxin is a biologically relevant pathological stimulus, we investigated the effect of endotoxin on alveolar epithelial liquid clearance in vivo. Escherichia coli endotoxin (220 micrograms/kg) was instilled into the lungs via the trachea of rats. Then, 24 or 40 h after endotoxin instillation, alveolar and lung liquid clearances were studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of 125I-labeled albumin (6 ml/kg into both lungs). Alveolar liquid clearance was significantly greater at 24 h (36 +/- 5%) and 40 h (38 +/- 7%) after endotoxin exposure than in saline-instilled controls (27 +/- 6%). Although there was an influx of neutrophils into the air space, there was no increase in lung epithelial permeability to protein at 24 or 40 h. Amiloride (2 x 10(-3) M), a sodium channel inhibitor, significantly reduced alveolar liquid clearance in the rats exposed to endotoxin. However, the increase in alveolar liquid clearance was not inhibited when propranolol (2 x 10(-5) M) was added to the 5% albumin solution. Thus exposure to alveolar endotoxin upregulates net alveolar fluid clearance in vivo for up to 40 h, a potentially important mechanism for accelerating alveolar fluid clearance under some pathological conditions. The increase in alveolar liquid clearance 24 and 40 h after instillation of endotoxin into the air spaces is mediated by an increased uptake of sodium through amiloride-sensitive sodium channels.
authors.affiliation: Department of Physiology, Hôpital Henri Mondor, Créteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Garat
authors.forename: S
authors.initials: S
authors.lastname: Rezaiguia
authors.forename: M
authors.initials: M
authors.lastname: Meignan
authors.forename: M P
authors.initials: MP
authors.lastname: D'Ortho
authors.forename: A
authors.initials: A
authors.lastname: Harf
authors.forename: M A
authors.initials: MA
authors.lastname: Matthay
authors.forename: C
authors.initials: C
authors.lastname: Jayr
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D006439:Hemodynamics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D000584:Amiloride