159 - Acute Pulmonary Nanoparticle Exposure Induces Middle Cerebral Artery Endothelial Dysfunction: Gender-Dependent Contribution of Xanthine Oxidase

Abstract

Engineered nanomaterials (ENM) are present in numerous activities; however, proper EMN toxicological assessments are typically incomplete. Previous studies demonstrate that ENM exposure is linked to adverse cardiovascular outcomes, including stroke. The cerebral microcirculation is essential for blood flow regulation in the brain and as such, dysfunction may augment the risk of stroke. The impact of pulmonary nano-titanium dioxide (TiO2) exposure on the cerebral microcirculation is unknown. To determine if acute nano-TiO2 exposure mediates microvessel endothelial dysfunction, intra-tracheal instillation was used to deliver 240 µg of nano-TiO2 to male and female Sprague-Dawley rats 24 h prior to surgery. The middle cerebral arteries (MCAs) were then isolated and assessed for vasoactivity to acetylcholine (ACh) or phenylephrine (PE). Since endothelial dysfunction can be induced by elevation in rates of oxidant generation, potentially via increased endothelium-associated xanthine oxidase (XO) activity, we then exposed MCAs to the XO-specific inhibitor, febuxostat (10 μM) for 30 min prior to ACh-induced dilation. Nano-TiO2 exposure decreased MCA endothelium-dependent dilation (p