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Effects of multiwalled carbon nanotube coincubation on vascular reactivity and nitric oxide (NO) availablility.
Stapleton-PG; McBride-CR; Chen-BT; Castranova-V; Nurkiewicz-TR
Toxicologist 2012 Mar; 126(Suppl 1):197
Multiwalled carbon nanotubes (MWCNT) are widely used in many fields to enhance existing materials for strength, conduction, and isolation. Most recently, their potential as a drug delivery mechanism and other biomedical applications has been investigated. Therefore, the inherent toxicity of MWCNT and their direct effects on microvascular tissue function were investigated. These effects were measured using a water jacketed biosensing chamber containing ISO-NOP NO probes connected to a free radical analyzer (WPI) to make direct electrochemical NO measurements. MWCNT in the chamber at concentrations of 100, 50, 25, 10, 5, and 1 microg/ml attenuated the amount of NO produced by the donor S-Nitroso-NAcetyl- D,L-Penicillamine (SNAP) by 4% + / - 1% to 59% + / - 6% inhibition of maximal [NO] sensed by the NO probes. This implies MWCNT have the ability to quench liberated NO. When microvessels isolated from the spinotrapezius muscle are present, co-incubation with MWCNT (100 microg/ml) leads to a 40% inhibition of NO signal after stimulation with a bolus dose of the Ca2+ ionophore A23187, implying a direct effect of MWCNT on the vessels ability to produce NO. Reactivity of sub-epicardial arterioles isolated from the left anterior descending artery distribution (approximately 170 microm in diameter) was also impaired with MWCNT co-incubation (100 microg/ml) compared to control maximum dilation based on responses to increasing concentrations of endothelium dependent agonists acetylcholine (38% +/- 6%) and A23187 (32% +/- 6%), indicating endothelium-dependent dilation (which relies heavily on NO) is altered. Collectively, these data indicate that MWCNT possess the potential to have a direct effect on liberated NO bioavailablilty and vascular NO production, leading to an impairment in arteriolar reactivity.
Nanotechnology; Health-hazards; Hazardous-materials; Toxic-materials; Biomedical-engineering; Drugs; Hospital-equipment; Medical-treatment; Medicinal-chemicals; Laboratory-animals; Laboratory-techniques; Laboratory-testing; Aerosol-particles; Air-flow; Particle-aerodynamics; Particle-counters; Exposure-levels; Cardiovascular-system; Heart; Tissue-culture; Tissue-disorders; Free-radicals; Measurement-equipment; Electrochemical-analysis; Electrochemical-reactions; Oxides
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California