Role of nitric oxide-derived oxidants in vascular injury from carbon monoxide in the rat

• Published in: American journal of physiology. Heart and circulatory physiology 1999-03, Vol.276 (3), p.H984-H992
• Main Authors: Thom, Stephen R, Fisher, Donald, Xu, Y. Anne, Garner, Sarah, Ischiropoulos, Harry
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1999.276.3.h984

1  Institute for Environmental Medicine and 2  Departments of Emergency Medicine and 3  Biochemistry and Biophysics, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6068 Studies were conducted with rats to investigate whether exposure to CO at concentrations frequently found in the environment caused nitric oxide (NO)-mediated vessel wall changes. Exposure to CO at concentrations of 50 parts per million or higher for 1 h increased the concentration of nitrotyrosine in the aorta. Immunologically reactive nitrotyrosine was localized in a discrete fashion along the endothelial lining, and this was inhibited by pretreatment with the NO synthase (NOS) inhibitor N -nitro- L -arginine methyl ester ( L -NAME). The CO-induced elevations of aortic nitrotyrosine were not altered by neutropenia or thrombocytopenia, and CO caused no change in the concentration of endothelial NOS. Consequences from NO-derived stress on the vasculature included an enhanced transcapillary efflux of albumin within the first 3 h after CO exposure and leukocyte sequestration that became apparent 18 h after CO exposure. Oxidized plasma low-density lipoprotein was found immediately after CO exposure, but this was not inhibited by L -NAME pretreatment. We conclude that exposure to relatively low CO concentrations can alter vascular status by several mechanisms and that many changes are linked to NO-derived oxidants. myeloperoxidase; nitrotyrosine; lipoprotein oxidation; endothelium; xanthine oxidase