Exposure to Nickel-Hydroxide Nanopartiles Alters Vascular Reactivity in C57BL/6 Mice

Azita Madrid (1), Eric Liberda (2), Lung Chi Chen (3)

(1) New York University Department of Environmental Medicine, Tuxedo NY, New York University Department of Environmental Medicine, Tuxedo NY (2), New York University Department of Environmental Medicine, Tuxedo NY (3)

     Abstract Number: 316
     Last modified: November 9, 2009

Abstract
There is growing interest in engineered nanoparticles (NPs) for various medical and technological applications, but the long term environmental and health effects of these NPs (particles with a diameter < 100 nm) are still being discovered. Since there have been associations reported between inhaled ambient ultrafine particles and increased risk of cardiopulmonary disease, it has been suggested that inhaled NPs may also induce adverse effects on the cardiovascular system. Acute exposure to Nickel NPs, specifically has been suggested to induce pulmonary and systemic inflammation and, long term studies demonstrate exacerbation of atherosclerosis in apoprotein E knockout (ApoE KO) mice. However the exact mechanisms are not well understood. Few of these studies have specifically measured vascular function, specifically, arterial vasoconstriction and endothelial dysfunction. Nickel hydroxide nanoparticles (NH-NPs) were used as a test material and thoroughly characterized for various physicochemical properties related to toxicity. A series of preliminary inhalation studies were conducted using wild-type C57BL/6 mice to identify acute toxic potential of NH-NPs. Utilizing a whole body inhalation exposure system, C57BL/6 mice were exposed for 1 or 3 days to either NH-NPs (diameter of primary particle: 5 nanometers, count median diameter of agglomerates: approximately 40 nanometers) at approximately 150 micrograms Ni/cubic meter (approximately 10% of the current occupational standard), or to filtered air. Carotid arteries were isolated from each animal and 2 millimeters segments were mounted on a tension myograph system to measure contractile response. Compared to the filtered air exposed mice, no significant differences in the contractile response to phenylephrine (PE) was observed at either time point. However, at both time points, data indicates a decrease in relaxation after administration of acytelcholine (ACh) as compared to the controls. The results suggest that short-term exposure to NH-NPs is associated with acute endothelial response and vasoconstriction and is consistent with similar findings from findings from studies examining aorta.