Time-course of impaired coronary arteriolar endothelium-dependent dilation after multi-walled carbon nanotube inhalation.
Stapleton-PG; Minarchick-VC; Cumpston-A; McKinney-W; Chen-BT; Frazer-D; Castranova-V; Nurkiewicz-TR
Toxicologist 2011 Mar; 120(Suppl 2):41
We have shown that exposure to fine particulate matter (PM), and more recently, nanoparticules, can lead to changes in reactivity within the skeletal muscle and coronary microvasculature. Multi-walled carbon nanotubes (MWCNT) are becoming widely used in many fields to enhance existing materials for strength, conduction, and isolation. Rats were exposed to filtered air (control) or MWCNT with count mode aerodynamic diameter of 420 nm via a single day 5-hour inhalation exposure (+/- 20 min) at concentrations of 26 +/- 2 mg/m3 which produced calculated pulmonary depositions of 22 +/- 2 ug. Coronary arterioles were isolated from the left anterior descending (LAD) artery distribution and isolated microvessel analysis of sub-epicardial arterioles (approximately 150 microm in diameter) was performed based on responses to transmural pressure and to increasing concentrations of phenylephrine (PE), acetylcholine (ACH), the Ca2+ ionophore A23187, and sodium nitroprusside (SNP) over a time course of 24, 72, 120, or 168 hours post MWCNT exposure. There were no significant differences observed in the endothelium-independent responses to SNP and PE indicating smooth muscle sensitivity to nitric oxide (NO) and adrenergic responses were intact. Vascular reactivity to increasing concentrations of ACH lead to significant differences from controls for each of the points within the post-exposure time course (24, 72, 120, and 168 hours) indicating that: 1) MWCNT inhalation impairs endothelium-dependent dilation and 2) this systemic microvascular effect lasts for at least one week post exposure. These findings are consistent with other nanoparticle outcomes in addition to the cardiac events described after PM exposure.
Biological-effects; Cardiopulmonary-function; Cardiopulmonary-system; Cardiopulmonary-system-disorders; Cell-biology; Cellular-reactions; Dose-response; Exposure-levels; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-function; Microscopic-analysis; Musculoskeletal-system; Nanotechnology; Particle-aerodynamics; Particle-counters; Particulates; Particulate-sampling-methods; Physiological-effects; Pulmonary-function; Pulmonary-system; Quantitative-analysis; Respiration; Statistical-analysis; Time-weighted-average-exposure
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC