Pulmonary inhalation of ultrafine TiO2 and cardiovascular effects: a neuronregulated pathway.
Kan-H; Wu-Z; Lin-Y; Chen-BT; Cumpston-JL; Kashon-ML; Munson-AE; Castranova-V
Toxicologist 2012 Mar; 126(Suppl 1):322-323
Inhalation of nano-sized air pollutant particles is a recognized risk factor for cardiovascular disease; however, the link between occupational nanoparticle exposure and adverse cardiovascular events remains unclear. We reported previously that pulmonary exposure of rats to ultrafine titanium dioxide (UFTiO2) enhances substance P synthesis in nodose ganglia, which was associated with an increased phosphorylation level of cardiac proteins. In the present study, we further investigated changes in cardiovascular function following pulmonary exposure to UFTiO2. Our study indicates that pulmonary exposure of rats to UFTiO2 (6 mg/m3) for 4 hours significantly increased heart rate and depressed diastolic function of the heart in response to isoproterenol. On the vascular side, pulmonary exposure to UFTiO2 elevated mean and diastolic blood pressure in response to norepinephrine. Pretreatment of the rats ip with the transient receptor potential (TRP) channel blocker, ruthenium red (2.5 mg/kg), not only inhibited substance P synthesis in nodose ganglia and the increased phosphorylation level in cardiac proteins, but also prevented the above cardiovascular changes induced by pulmonary exposure to UFTiO2. Our results suggest that the effects of pulmonary exposure to UFTiO2 on the cardiovascular system are most likely influenced by a lung-nodose gangliaregulated pathway via the activation of TRP channels located on the endings of c fiber sensory neurons in the lung. Activation of this neuronal pathway may contribute to an increased incidence of cardiovascular diseases associated with pulmonary inhalation of small-sized particle components from ambient air.
Laboratory-animals; Laboratory-techniques; Laboratory-testing; Exposure-assessment; Exposure-methods; Exposure-levels; Lung; Pulmonary-system; Immune-reaction; Dose-response; Particulates; Nanotechnology; Cardiovascular-disease; Cardiovascular-function; Cardiovascular-system; Cardiovascular-system-disease; Heart
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California