Recently our collaborative group identified multi-walled carbon nanotube (MWCNT) translocation from the lung to the heart, liver, and kidneys within 24 hours after pulmonary exposure. From this finding, we continued to examine the microvascular ramifications associated with this direct interaction. To model drug delivery platforms, as well as lung migration, MWCNT were injected into the tail vein of rats (25-900 microg, suspended in 900 microL normosol). 24-hours later, coronary arterioles (<170 microm in diameter) from the left anterior descending artery distribution were isolated for reactivity assessments based on responses to transmural pressure (myogenic responsiveness), intraluminal flow (shear stress), phenylephrine (10-9-10-4 M), acetylcholine (10-9-10-4 M), A23187 (10-9-10-5 M), and spermineNONOate (10-9-10-4 M). Myogenic responsiveness was not altered after MWCNT injection. However, MWCNT injection at all concentrations robustly attenuated reactivity. The coronary microvascular dysfunction associated with MWCNT injection is significant, impacting endothelium-dependent, -independent, adrenergic, and flow-mediated dilation pathways. These alterations, in combination with previous findings, indicate that the microvascular impairments that follow MWCNT injection are more severe than those observed after ingestion or inhalation exposure. Studies are currently underway to further evaluate mechanistic differences between these routes of exposure.
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas