Formation of VascularS-Nitrosothiols and Plasma Nitrates/Nitrites Following Inhalation of Diesel Emissions

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/m3 of particulate matter (containing 3.5 ppm NO) or 0, 3, or 10 ppm NO as a positive control. Animals were also pre-injected (i.p.) with either saline or n-acetyl-cysteine (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 hr post-exposure. Whole DE exposure for 1 hr 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 NOS by 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.

Altered Nitric Oxide Bioavailability Contributes to Diesel Exhaust Inhalation‐Induced Cardiovascular Dysfunction in Man

“…Knuckles and colleagues have recently reported that following diesel exhaust exposure, rats had increased plasma NO x (nitrate and nitrite combined) concentrations that appeared to be predominantly the result of absorption of NO from the exposure itself, although they exhibited significant increases in eNOS expression consistent with increased NO production. 38 Controlled exposures to NO and nitrogen dioxide in humans with subsequent measurements of plasma nitrite concentrations may help to define this further.…”

Oxidative Stress, Inflammatory Biomarkers, and Toxicity in Mouse Lung and Liver after Inhalation Exposure to 100% Biodiesel or Petroleum Diesel Emissions

“…Reductions in pulmonary function have also been reported following occupational exposures in chronic studies (Rudell et al, 1996). In addition, diesel PM has been associated with changes in heart rate, increased incidence of arrhythmias, impairment of vasodilation, increase in blood pressure, and systemic inflammation (Hazari et al, 2011;Peretz et al, 2008;Tornqvist et al, 2007;Nemmar et al, 2007;Carll et al, 2013;Harkema et al, 2009;Knuckles et al, 2011). Human studies by Mills et al (2005Mills et al ( , 2007aMills et al ( , 2007b) demonstrated a dose-dependent increase in prothrombotic effects and acute myocardial ischemia upon exposure to diesel exhaust.…”

“…Previous studies focusing on the mechanisms of the effects of diesel CE exposure were performed using the following concentrations: 500 μg/m 3 and 300 μg/m 3 in rats (Carll et al, 2013;Carll et al, 2012;Harkema et al, 2009), and 300 μg/m 3 in mice (Knuckles et al, 2011). In particular, Finch et al (2002) exposed F344 rats to biodiesel at concentrations of 40, 200, and 500 μg/m 3 .…”

Whole and Particle-Free Diesel Exhausts Differentially Affect Cardiac Electrophysiology, Blood Pressure, and Autonomic Balance in Heart Failure–Prone Rats

“…Both DE groups had decreased BP during exposure, suggesting mediation by DE gases. Although the specific gases mediating this effect remain unclear, there is mounting evidence that inhaled NO is converted to nitric oxide (NOx), which remains in the blood up to 2 h postexposure (Knuckles et al, 2011). NOx decreases BP through vasodilation and facilitates parasympathetic control over cardiac function (Conlon and Kidd, 1999;Yabe et al, 1998).…”