Title: Formation of vascular S-nitrosothiols and plasma nitrates/nitrites following inhalation of diesel emissions.
Authors: Knuckles, Travis L; Buntz, Jennifer G; Paffett, Michael; Channell, Meghan; Harmon, Molly; Cherng, Tom; Lucas, Selita N; McDonald, Jacob D; Kanagy, Nancy L; Campen, Matthew J
Published In J Toxicol Environ Health A, (2011)
Abstract: Epidemiological studies have associated traffic-related airborne pollution with adverse cardiovascular outcomes. Nitric oxide (NO) is a common component of fresh diesel and gasoline engine emissions that rapidly transforms both in the atmosphere and once inhaled. Because of this rapid transformation, limited information is available in terms of potential human exposures and adverse health effects. Young rats were exposed to whole diesel emissions (DE) adjusted to 300 μg/m(3) of particulate matter (containing 3.5 ppm NO) or 0, 3, or 10 ppm NO as a positive control. Animals were also pre-injected (ip) with either saline or N-acetylcysteine (NAC), a precursor of glutathione. Predictably, pure NO exposures led to a concentration-dependent increase in plasma nitrates compared to controls, which lasted for roughly 4 h postexposure. Whole DE exposure for 1 h also led to a doubling of plasma NOx. NAC injection increased the levels of plasma nitrates and nitrites (NOx) in the DE exposure group. Inhibition of nitric oxide symthase (NOS) by N(G)-nitro-L-arginine (L-NNA) did not block the rise in plasma NOx, demonstrating that the increase was entirely due to exogenous sources. Both DE and pure NO exposures paradoxically led to elevated eNOS expression in aortic tissue. Furthermore, coronary arterioles from NO-exposed animals exhibited greater constriction to endothelin-1 compared to controls, consistent with a derangement of the NOS system. Thus, NO may be an important contributor to traffic-related cardiovascular morbidity, although further research is necessary for proper hazard identification.
PubMed ID: 21598168
MeSH Terms: Animals; Aorta/chemistry; Coronary Vessels/chemistry*; Coronary Vessels/metabolism; Dose-Response Relationship, Drug; Glutathione/metabolism; Inhalation Exposure/adverse effects; Male; Nitrates/analysis; Nitrates/blood*; Nitric Oxide Synthase/metabolism; Nitric Oxide/adverse effects; Nitric Oxide/blood; Nitric Oxide/metabolism; Nitrites/analysis; Nitrites/blood*; Rats; Rats, Sprague-Dawley; S-Nitrosothiols/analysis*; S-Nitrosothiols/blood; Vehicle Emissions/toxicity*