Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity

Abstract

Ambient ozone (O3) levels are associated with cardiovascular morbidity and mortality, but the underlying pathophysiological mechanisms driving extrapulmonary toxicity remain unclear. This study examined the coronary vascular bed of rats in terms of constrictive and dilatory responses to known agonists following a single O3 inhalation exposure. In addition, serum from exposed rats was used in ex vivo preparations to examine whether bioactivity and toxic effects of inhaled O3 could be conveyed to extrapulmonary systems via the circulation. We found that 24 h following inhalation of 1 ppm O3, isolated coronary vessels exhibited greater basal tone and constricted to a greater degree to serotonin stimulation. Vasodilation to acetylcholine (ACh) was markedly diminished in coronary arteries from O3-exposed rats, compared with filtered air-exposed controls. Dilation to ACh was restored by combined superoxide dismutase and catalase treatment, and also by NADPH oxidase inhibition. When dilute (10%) serum from exposed rats was perfused into the lumen of coronary arteries from unexposed, naïve rats, the O3-induced reduction in vasodilatory response to ACh was partially recapitulated. Furthermore, following O3 inhalation, serum exhibited a nitric oxide scavenging capacity, which may partially explain blunted ACh-mediated vasodilatory responses. Thus, bioactivity from inhalation exposures may be due to compositional changes of the circulation. These studies shed light on possible mechanisms of action that may explain O3-associated cardiac morbidity and mortality in humans.

MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor

“…Electron paramagnetic resonance (EPR) spectroscopy was conducted according to previously described methods with some modifications (Paffett et al , 2015). Following serum treatment, mCECs were incubated with the iron-chelate NO-spin trap Fe 2+- di( N -methyl- d -glutaminedithiocarbamate) (Fe 2+ (MGD) 2 ; 1mM, final concentration) for 5min.…”

Metabolomic profiles of plasma, exhaled breath condensate, and saliva are correlated with potential for air toxics detection

“…However, the toxic effects of exposure to airborne total particulate matter (PM) from primary TRP have been demonstrated (11–14). These toxic effects range from increased short-term morbidity in individuals with preexisting respiratory and cardiovascular disease to excess mortality rates over life-long exposure durations (15, 16).…”

Spatiotemporal Patterns of Ozone and Cardiovascular and Respiratory Disease Mortalities Due to Ozone in Shenzhen

“…Numerous epidemiology studies have shown the association between ozone exposure and respiratory and cardiovascular diseases [2,5,29]. Inhaled ozone could cause decreased lung function and increased airway hyper-reactivity, particularly for those with preexisting conditions [11,30]. A recent study using the rat experiment model suggested that ozone exposure could lead to significant perturbations of coronary vascular functions possibly related to intracellular redox disturbances [31].…”