title: NO prevents neutrophil-mediated pulmonary vasomotor dysfunction in acute lung injury.
abstract: The purpose of this study was to examine the effect of administration of inhaled nitric oxide (NO) on lung neutrophil accumulation and pulmonary vascular endothelial cell function in endotoxin-induced acute lung injury. Mechanically ventilated rats were studied 4 hr after endotoxin (0.5 mg/kg IP). Inhaled NO (20 ppm) was administered for either the entire 4 hr after endotoxin (continuous group) or for only the first 2 of 4 hr after endotoxin (abbreviated group). Endothelial-dependent (acetylcholine, ACh) and -independent cGMP-mediated relaxation (nitroprusside, SNP) pulmonary vasorelaxation were studied in isolated pulmonary arterial rings. Lung neutrophil accumulation was determined by myeloperoxidase assay (MPO). Inhaled NO prevented endotoxin-induced lung neutrophil accumulation as well as pulmonary endothelial cell dysfunction. However, this protection required continuous administration of inhaled NO. We conclude that inhaled NO prevents neutrophil-mediated pulmonary vascular endothelial cell dysfunction in acute lung injury.
authors.affiliation: University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Friese
authors.forename: D A
authors.initials: DA
authors.lastname: Fullerton
authors.forename: R C
authors.initials: RC
authors.lastname: McIntyre
authors.forename: T F
authors.initials: TF
authors.lastname: Rehring
authors.forename: J
authors.initials: J
authors.lastname: Agrafojo
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D004731:Endotoxins / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D004731:Endotoxins; D009599:Nitroprusside; D009569:Nitric Oxide; D009195:Peroxidase; D006152:Cyclic GMP; D000109:Acetylcholine