However, the absolute content of Si in the eastern U.S. is quite low, whereas sulfate is the predominate non-carbon constituent [19]. In our particulate sample, the content of Si is second only to sulfate in terms of% of total mass. Si is a known respiratory toxicant and has been implicated in specific diseases in miners such as coal workers pneumoconiosis [7], which has been observed at surface mines in the United States [8]. Furthermore, selleck kinase inhibitor silica particle exposures have been demonstrated to reduce HR

variability measures in mice suggesting cardiotoxic effect [9]. The dosage of 300 μg per rat used in this study is a typical toxicological dosage to determine effect in healthy animals. Furthermore, this dosage, which is ~1 mg/kg, is lower than previous dosages used by our group [34], and lower than the dosages reported by other groups for initial determination of toxic effects [10]. Furthermore, the single-dose exposure in rats reported here would be equivalent to an accumulated dose over the course of 1.7 years based on ambient recorded concentrations of PM10 of 8.3 µg/m3 a minute ventilation www.selleckchem.com/products/PLX-4032.html of 200 mL/min, and an estimated deposition fraction of 0.2. While high, these dosages represent an accumulated dosage based on a low average ambient particle concentrations that are approximately double that of ambient concentrations

determined in non-mining areas (data not shown). Additionally, this study is a toxicological determination of an effect from which future work will determine dose response and temporal relationships. Arteriolar tone, in vivo, is generated by the complex interplay between intrinsic and extrinsic factors [41]. In this study, PMMTM exposure

altered resting tone in the l-NMMA-treated arterioles (Table 3), which contrasts with previous findings in our laboratory [24]. Alteration of diameter or tone following l-NMMA treatment in the arteriolar network of the spinotrapezius is inconsistent between studies, with some investigations demonstrating an increase in arteriolar tone [28], while others show no change [24]. Metabolically stimulated vasodilation buy 5-Fluoracil by AH was not found to be significantly different between the sham and PMMTM-exposed groups (Figure 3A). These data are not consistent with previous exposures performed in our laboratory using TiO2 nanoparticles in which we demonstrated a marked decrease in vasodilation at 12 Hz [24], suggesting that AH-mediated arteriolar dilation is not impaired following PMMTM exposure. However, during NOS inhibition (l-NMMA), it becomes apparent that the mechanisms supporting AH after PMMTM exposure are altered (Figure 3A). Because NOS inhibition did not affect AH in the PMMTM group, other vasoactive influences, such as COX products, may be compensating to preserve normal reactivity to this metabolic stimulus. In previous work, we have demonstrated such a compensatory mechanism [24, 27].