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Systemic disposition of inhaled nitric oxide, a significant somponent of vehicular emissions
Citation:
KNUCKLES, T., A. K. LUND, S. Lucas, M. C. MADDEN, AND M. J. CAMPEN. Systemic disposition of inhaled nitric oxide, a significant somponent of vehicular emissions. Presented at Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
research results
Description:
Epidemiological studies have associated airborne pollution with adverse cardiovascular outcomes. Furthermore, air pollution-associated gases, primarily from mobile source emissions (e.g. NOx), have been linked to increased cardiovascular death. A mechanism for these effects has not been elucidated and remains under investigation. Rats were exposed to whole diesel emissions (DE) adjusted to 300 µg/m3 of particulate matter, filtered air (FA), or 10 ppm nitric oxide (NO) as a positive control. Animals exposed to DE and FA groups were also pre-injected with either saline or 200 µM/kg n-acetyl-cysteine (NAC) a known scavenger of NO. Following 1 or 2 h of exposure, plasma NOx, a measure of total NO, were determined. Predictably, pure NO exposures lead to a doubling of plasma NOx from 4 µM in the FA group to 10 µM in the DE group. Whole DE for 1 h also lead to a doubling of plasma NOx with NAC paradoxically increasing the levels of plasma NOx in the DE exposure group. The increase in plasma NOx was accompanied with an increase in plasma reactive oxygen species. Furthermore, an increase in plasma NOx was also seen following 2 h of exposure but without a significant increase in the NAC pretreated animals which was likely because the T1/2 of NAC is ~45 min in the body. In a separate series of experiments, human subjects were exposed to DE or FA on separate occasions for two hours and plasma was taken immediately following exposure and 20 h post-exposure. Plasma NOx was increased immediately following exposure compared to FA and this increase was resolved 20 h post-exposure. These data suggest that the increase in plasma NOx in the NAC treated animals is likely though s-nitrosylation of NAC, thereby sequestering free NO and leading to a reduction in nitrosative stress. Thus, inhaled NO may be more likely to promote nitrosative stress in individuals with low levels of thi