Inhaled nitric oxide down-regulates intrapulmonary nitric oxide production in lipopolysaccharide-induced acute lung injury.
OBJECTIVE
To examine whether inhaled nitric oxide (NO) affected the intrapulmonary production of NO, reactive oxygen species, and nuclear factor-kappaB in a lipopolysaccharide (LPS)-induced model of acute lung injury.


METHODS
Prospective, randomized, laboratory study.


METHODS
Experimental laboratory at a biomedical institute.


METHODS
Twenty male rabbits weighing 2.5-3.5 kg.


METHODS
Saline or LPS (5 mg/kg of body weight) was administered intravenously with or without NO inhalation (10 ppm) in each group of five rabbits.


RESULTS
LPS increased the lung leak index, the neutrophils and NO levels in bronchoalveolar lavage fluid, and NO levels produced by resting and stimulated alveolar macrophages. Inhaled NO decreased the lung leak index, the neutrophils and NO levels as measured by nitrite levels in the lavage fluid, and NO produced by the resting and stimulated alveolar macrophages. Inhaled NO also blocked the activities of reactive oxygen species and nuclear factor-kappaB binding to DNA in lavage cells and in alveolar macrophages.


CONCLUSIONS
Inhaled NO attenuates LPS-induced acute lung injury, possibly by decreasing NO production in the lungs. The mechanism of reducing NO production resulting from inhaled NO may involve, in part, the activities of reactive oxygen species and/or nuclear factor-kappaB.
Koh
Y
Y
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap Dong Songpa Ku, Seoul 138-736, Korea. yskoh@www.amc.seoul.kr
Kang
J L
JL
Park
W
W
Pack
I S
IS
Lee
H S
HS
Kim
M J
MJ
Lim
C M
CM
D000208:Acute Disease; D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D008070:Lipopolysaccharides; D008163:Luminescent Measurements; D008168:Lung / Q000378:metabolism*; D055370:Lung Injury; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide