title: Sepsis and hyperoxia effects on the pulmonary surfactant system in wild-type and iNOS knockout mice.
abstract: Alterations of pulmonary surfactant and increases in inducible nitric oxide synthase (iNOS) have been implicated in the pathophysiology of acute lung injury. It was hypothesised that these two observations are related and that alterations of the endogenous surfactant, due to either sepsis or hyperoxia, would be reduced in mice lacking the iNOS gene compared to wild-type mice. Wild-type and iNOS (-/-) mice were randomised into sham or sepsis, and in a separate experiment animals were randomised to normoxia or hyperoxia exposure for 48 h. Lungs were lavaged and analysed for total surfactant levels and surfactant subfractions (large (LA) and small (SA) aggregates). Both sepsis groups had decreased SA compared to sham groups with no significant difference between the two genotypes. Mice exposed to hyperoxia had a decreased amount of total surfactant when compared to normoxia controls and there was no significant difference between the two genotypes. It is concluded that inducible nitric oxide synthase does not influence the amount of pulmonary surfactant or surfactant subfractions recovered in lavage after 18 h of sepsis or 48 h of hyperoxia.
authors.affiliation: Dept of Physiology, Lawson Health Research Institute, University of Western Ontario, London, Canada. tbailey2@uwo.ca
authors.forename: T C
authors.initials: TC
authors.lastname: Bailey
authors.forename: C
authors.initials: C
authors.lastname: Cavanagh
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: J F
authors.initials: JF
authors.lastname: Lewis
authors.forename: R A W
authors.initials: RA
authors.lastname: Veldhuizen
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000150:complications* / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II; D011663:Pulmonary Surfactants / Q000032:analysis* / Q000737:chemistry; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000201:enzymology* / Q000209:etiology*; D018805:Sepsis / Q000150:complications* / Q000201:enzymology*; D013997:Time Factors
chemical_list: D011663:Pulmonary Surfactants; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse