Own to mediate vasoconstriction in aorta tissue [12,54]. This effect of hydrogen
Own to mediate vasoconstriction in aorta tissue [12,54]. This effect of hydrogen peroxide would be associated with reduced vasodilatory response in our experiment. It seems PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26552366 that the tempol treatment has different effect in healthy and aged/diseased vessels. This possibly limits the extrapolation of our results to effects of tempol-generated hydrogen peroxide in aged/diseased vessels and firm conclusions about the possible role of hydrogen peroxide may require co-incubation with compounds that removes it (e.g. catalase). Our investigation showed no effect of pulmonary exposure of TiO2 particle with different physicochemical characteristics on the vasodilatory Pan-RAS-IN-1 molecular weight function in aorta or mRNA expression of genes relevant in the inflammatory response in the lung, whereas the effect of one form on plaques progression was modest. Therefore, the outcome of the investigation is not optimal for assessment of the importance of particle size or composition or dose. We used mass doses and exposure protocols of TiO2 in ApoE-/- mice similar to what had shown significant effect for carbon black and SWCNT in terms of vasodilation function and plaque progression, respectively [25,42]. However, a direct dose comparison as mass burden or even surface area, between TiO2 particles and SWCNT does not take the overt differences in structure and reactivity into account. The latter exposure was associated with pulmonary inflammatory reaction, systemic oxidative stress and mitochondrial dysfunction, whereas minimal systemic inflammation was detected [25]. TiO2 and carbon black are regarded as “low-solubility low-toxicity” particles with similar inflammogenic potency per instilled surface area [55,56]. Indeed, we also found little pulmonary inflammation at doses that were four times larger than the individual doses of fTiO2 and nTiO2, whereas there was a linear relationship between the surface area and inflammation in relation to fine and nanosized carbon black after a single large-dose exposure [22]. The fTiO2 and nTiO2 samples in our study also had rutile crystal structure and surface coating, whereas pTiO 2 was an uncoatedmixture of anatase and rutile structure. It has been argued that the anatase crystal structure of TiO2 might be more reactive and cytotoxic as compared to rutile crystal structure [57]. In addition, the dispersion protocols might have an influence; some studies on TiO2 use dispersions in saline solution [36]. We used BAL fluid, which provides a well dispersed suspension of nanosized TiO2 and it has been shown to cause pulmonary inflammation after i.t. instillation in rats, whereas poorly dispersed nanosized TiO2 suspensions in saline had similar inflammogenic potency as fine TiO 2 particles in rats after i.t. instillation [58,59]. However, suspensions in BAL fluid may also lead to formation of a protein corona on the particles, which may change the particle surface chemistry, although we cannot predict whether our TiO 2 particles would be less potent by coating with proteins.Conclusions We show for the first time that pulmonary exposure to nanosized TiO2 is associated with a modest increase in plaque progression. On the other hand, three physicochemically different TiO 2 nanomaterials (including nanosized TiO2) have virtually no effect on vasodilation induced from either endothelial or smooth muscle cells at exposure levels that were not associated with increased Mcp-1 and Mip-2 expression. Materials and methodsParticlesThe following materials were.