title: Pulmonary vascular stress from carbon monoxide.
abstract: 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.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104-6068, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Thom
authors.forename: S T
authors.initials: ST
authors.lastname: Ohnishi
authors.forename: D
authors.initials: D
authors.lastname: Fisher
authors.forename: Y A
authors.initials: YA
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: 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*
chemical_list: 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