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)-N-.)-derived oxidants. Lung capi llary 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)-N-. during CO exposure was demonstrated by electron paramagnetic resonance spe ctroscopy. There was a 2.6-fold increase of (NO)-N-. over control in the lu ngs of rats exposed to 100 ppm CO. A qualitative increase in the concentrat ion of H2O2 was also detected in lungs during CO exposure, and this change was caused by (NO)-N-. as it was inhibited in rats pretreated with the nitr ic oxide synthase inhibitor, N-omega nitro-L-arginine methyl ester (L-NAME) . Production of (NO)-N-.-derived oxidants during CO exposure was indicated by an elevated concentration of nitrotyrosine in lung homogenates. The CO-a ssociated elevations in lung capillary leakage and nitrotyrosine concentrat ion did not occur when rats were pretreated with L-NAME. CO exposure did no t change the concentrations of endothelial or inducible nitric oxide syntha se in lung and leukocyte sequestration was not detected as a consequence of CO exposure. CO-mediated lung leak and nitrotyrosine elevation were not af fected by neutropenia. We conclude that CO exposure elevates the steady-sta te concentration of (NO)-N-. in lungs. Consequences from this change includ e increases in the concentration of reactive oxygen species, production of (NO)-N-.-derived oxidants such as peroxynitrite, and physiological evidence of lung injury. (C) 1999 Academic Press.