NO prevents neutrophil-mediated pulmonary vasomotor dysfunction in acute lung injury.
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.
Friese
R S
RS
University of Colorado Health Sciences Center, Denver 80262, USA.
Fullerton
D A
DA
McIntyre
R C
RC
Rehring
T F
TF
Agrafojo
J
J
Banerjee
A
A
Harken
A H
AH
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
D004731:Endotoxins; D009599:Nitroprusside; D009569:Nitric Oxide; D009195:Peroxidase; D006152:Cyclic GMP; D000109:Acetylcholine