Pulmonary vascular stress from carbon monoxide.
Studies were conducted with rats to investigate whether exposure to carbon monoxide (CO) at concentrations frequently found in the environment caused lung injury mediated by nitric oxide (*NO)-derived oxidants. Lung capillary leakage was significantly increased 18 h after rats had been exposed to CO at concentrations of 50 ppm or more for 1 h. An elevation of *NO during CO exposure was demonstrated by electron paramagnetic resonance spectroscopy. There was a 2.6-fold increase of *NO over control in the lungs of rats exposed to 100 ppm CO. A qualitative increase in the concentration of H2O2 was also detected in lungs during CO exposure, and this change was caused by *NO as it was inhibited in rats pretreated with the nitric oxide synthase inhibitor, Nomega nitro-l-arginine methyl ester (l-NAME). Production of *NO-derived oxidants during CO exposure was indicated by an elevated concentration of nitrotyrosine in lung homogenates. The CO-associated elevations in lung capillary leakage and nitrotyrosine concentration did not occur when rats were pretreated with l-NAME. CO exposure did not change the concentrations of endothelial or inducible nitric oxide synthase in lung and leukocyte sequestration was not detected as a consequence of CO exposure. CO-mediated lung leak and nitrotyrosine elevation were not affected by neutropenia. We conclude that CO exposure elevates the steady-state concentration of *NO in lungs. Consequences from this change include increases in the concentration of reactive oxygen species, production of *NO-derived oxidants such as peroxynitrite, and physiological evidence of lung injury.
Thom
S R
SR
Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104-6068, USA.
Ohnishi
S T
ST
Fisher
D
D
Xu
Y A
YA
Ischiropoulos
H
H
D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002248:Carbon Monoxide / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D007962:Leukocytes / Q000502:physiology; D008168:Lung / Q000098:blood supply*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000378:metabolism; D014652:Vascular Diseases / Q000139:chemically induced*
D004791:Enzyme Inhibitors; D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; D014443:Tyrosine; D002248:Carbon Monoxide; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester