[abstract] VASCULAR NITROSATIVE STRESS FROM CO EXPOSURE

Abstract

BACKGROUND: Studies have indicated that some aspects of CO and nitric oxide (NO) toxicity overlap. We hypothesized that rats exposed to even relatively low concentrations of CO would exhibit evidence of vascular stress due to NO-derived oxidants. METHODS: Rats were exposed for 1 hour to 0 and 1000 ppm CO and nitrotyrosine, a "foot print" of peroxynitrite-mediated stress, was assayed in aortas immediately afterward. RESULTS: CO caused NO- mediated stress based on an increase in nitrotyrosine, which did not correlate with carboxyhemoglobin (COHb) level. Nitrotyrosine was localized to the endothelial lining, and formation was inhibited with the nitric oxide synthase inhibitor, L-NAME. *&+, p<0.05 vs control values Aortic nitrotyrosine level was not altered in neutropenic or thrombocytopenic rats. Western analysis indicated no change in total nitric oxide synthase from control aortas. Myeloperoxidase concentration in aortas was elevated 24 hours after CO exposure. CONCLUSION: Endothelial cells, themselves, appear to be the source of NO-derived oxidants and leukocyte sequestration was a consequence of NO mediated stress.