SAN FRANCISCO — Exposure to nano-sized particles can impair the responsiveness of very tiny blood vessels, new animal studies show.
Vessels called arterioles don’t dilate or constrict appropriately after recent nanoparticle exposure. The changes are small “but equate to a level of impairment that would preclude affected tissues from functioning normally,” says microvascular physiologist Timothy Nurkiewicz of West Virginia University in Morgantown.
His team described new experiments March 13 at the Society of Toxicology annual meeting.
The West Virginia researchers “have a unique set of findings that are pretty powerful,” says Alex Carll, a toxicologist at the University of North Carolina at Chapel Hill. Their data “offer further demonstration that air pollutants can impair cardiac function.”
In one set of tests, physiologist Travis Knuckles of West Virginia University exposed rats to airborne titanium dioxide nanoparticles — spheres 100 billionths of a meter across — for four hours on two consecutive days. The common material appears in a range of materials, including sunscreen and cosmetics. The pollutant doses, though not in a range considered toxic, were high enough to probe the possible effects of occupational exposures to such engineered materials and nano-pollutants associated with mountaintop mining.
Twenty-four hours after the second day’s exposure, Knuckles stimulated the animals’ muscles to contract. This triggers arteriole dilation, increasing blood flow. But compared to changes witnessed in rats that had breathed only clean air, vessel dilation in those that had inhaled nanoparticles was impaired.
This diminished vessel relaxation is similar to what elicits a muscle cramp, chest pain in the heart or transient stroke in the brain, Nurkiewicz explains.
In another experiment, rats inhaled or ingested particles known as multi-walled carbon nanotubes. Made from rolled up sheets of carbon, these tubes are about 50 billionths of a meter across and being explored for use in delivering drugs via the nose, mouth or injections. As with the nanospheres, the nanotubes made it harder for arterioles to dilate. The nanotubes also exaggerated constriction when the body commanded arterioles to reduce blood flow.
Effects peaked at about 24 hours after exposure to the particles, after which the arterioles’ responsiveness began to improve. However, even a week later, the vessels hadn’t fully returned to normal, reported Phoebe Stapleton, a toxicologist on the West Virginia team.
Moreover, the findings showed that vessel impairments did not require lung exposures: In these experiments, ingested nanotubes produced the most dramatic change in arteriole reactivity.
Other teams at the meeting reported preliminary evidence of toxic immune responses in animals and isolated cells to other nanoparticles being developed for releasing medicines. Taken together, Nurkiewicz says, these new data suggest researchers should consider not only how much of a nano-delivered drug to give, but also the recipe of the nanomaterial used to ferry it.