Metal rich particulate matter impairs acetylcholine-mediated vasorelaxation of microvessels in mice
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RESEARCH
Open Access
Metal rich particulate matter impairs acetylcholine-mediated vasorelaxation of microvessels in mice Azita K Cuevas1, Jingping Niu2, Mianhua Zhong1, Eric N Liberda1, Andrew Ghio3, Qingshan Qu1 and Lung Chi Chen1*
Abstract Background: Exposure to PM2.5 (particulate matter 400 μm). However, the microcirculation is the primary site of vascular resistance and nutrient and waste exchange in the body. Perturbations in microvascular vasoreactivity can have profound impact on tissue perfusion, and ultimately homeostasis [24]. Since microcirculation takes place in the small resistance vessels (40–100 μm of lumen diameter) and regulates blood/oxygen flow and pressure to and from the tissues, they provide a good contrast to the larger, systematic conduit vessels, like the aorta. Hence, the aim of this study was two-fold: to use the PM2.5 samples collected from these cities to further explore the role of Ni found in PM and; to utilize this particulate to determine the underlying mechanism(s) of arteriolar function in the small resistance vessels of a mouse model following PM2.5 exposure. We hypothesized that exposure to PM2.5 rich in Ni alters arteriolar reactivity through mechanistic pathways involved in endothelium-dependent arteriolar dilation in the mesenteric arteries, of eNOS uncoupling and NADPH oxidase activation, leading to vascular ROS generation and vascular dysfunction.
Results Particle characterization
The particle characterization and analysis is described by Niu et al. [21]. In brief, PM2.5 mass measurements were not significantly different between JC (43.0 ± 40.7 μg/m3) and ZH (45.5 ± 47.7 μg/m3). The PM2.5 levels in both locations were approximately twice as high as the annual averages (20.2 ± 13.3 μg/m3) observed in New York City [25]. However, the ambient level of Ni measured in the JC location (204.8 ± 268.6 ng/m3) was 76-fold higher than that measured in ZH (2.8 ± 4.4 ng/m3). The sulfate form of the metals were selected for spiking since sulfur was high in the PM samples and also because sulfates are soluble and hence they are good candidates to investigate as drivers of the observed effects. Bronchoalveolar Lavage Fluid (BALF) characterization
Protein leakage (Figure 1A), neutrophil infiltration (Figure 1B), and cell count (Figure 1C), results from BALF analysis from a single aspiration dose of 50 μg/ mouse (1 mg/ml) revealed pulmonary inflammation. Specifically, protein leakage from mice treated with ZH was significantly higher than control; however, JC caused the greatest pulmonary inflammation. Particles from ZH spiked with one or all of the four metals found in the same concentrations as seen in the JC sample (As, Se, Cu, and Ni) demonstrated an increase in protein leakage (Figure 1A). Although there could be countless combinations of metals that could be studied, for the purposes of this study we decided to focus on the one that had the greatest inflammatory effects. Specifically, Ni was of greatest interest due to previous
Cuevas et al. Particle and Fibre Toxicology (2015
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