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Pulmonary nanoceria exposure impairs coronary and mesenteric arteriolar reactivity.
Minarchick-V; Stapleton-P; Porter-D; Sabolsky-E; Nurkiewicz-T
Toxicologist 2012 Mar; 126(Suppl 1):198
Ceria oxide (CeO2) is a common fuel catalyst that is present in resultant emissions. However, the health effects of inhaled nano-CeO2 are unknown. We have shown that pulmonary CeO2 exposure reduces endothelium-dependent and -independent arteriolar dilation. However, an effective concentration (EC50) has not been determined. The aim of this study was to determine the EC50 in Sprague-Dawley rats after nano-CeO2 exposure. Rats were intratracheally instilled with CeO2 at 0, 10, 50, 100, 200, and 400 microg/rat. The CeO2's primary diameter was approximately 3 nm (determined via transmission electron microscopy). 24 hours post exposure, the rats were anesthetized, the heart and mesentery were removed or bronchoalveolar lavage was performed to assess pulmonary inflammation. Arterioles (<150 microm) were dissected and prepared for isolated vessel experiments. Arteriolar reactivity was assessed by evaluating endothelium-dependent [A23187 (10-9-10-5 M) and acetylcholine (ACh, 10-9-10-4 M)], and -independent dilation [spermine NONOate (SPR, 10-9- 10-4 M)], vasoconstriction (seratonin, 10-9-10-4 M), and myogenic responsiveness (0-105 mmHg). In the sham-controls A23187, ACh and SPR caused a dose dependent dilation up to 60, 50, and 70% of the maximum diameter. After CeO2 exposure, this dilation was impaired by up to 75% (A23187), 43% (ACh), and 70% (SPR). Seratonin treatment produced robust constrictions in both arteriolar beds and CeO2 exposure did not significantly alter this. Coronary myogenic responsiveness was not altered by CeO2 exposure; whereas it was in mesenteric arterioles from rats exposed to 50 and 200 microg CeO2. These findings suggest that after CeO2 exposure, arteriolar dysfunction occurs in both microvascular beds studied, but this dysfunction is not identical. Moreover, these alterations in reactivity appear to be different from those observed after other nanoparticle exposures.
Oxides; Catalysis; Fuels; Nanotechnology; Laboratory-animals; Laboratory-techniques; Laboratory-testing; Exposure-assessment; Exposure-methods; Exposure-levels; Heart; Lung; Pulmonary-system; Immune-reaction; Dose-response; Vasoactive-agents; Particulates
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
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Content source: National Institute for Occupational Safety and Health Education and Information Division