Nanoparticle Inhalation Impairs Coronary Microvascular Reactivity via a Local Reactive Oxygen Species-Dependent Mechanism
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We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO2 nanoparticles via inhalation to produce a pulmonary deposition of 10 μg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with NG-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO2 exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated ACh-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO2. Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO2, but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range.
KeyWordsMicrocirculation Nanoparticle Coronary Arteriole Vasodilation Titanium dioxide Inhalation Reactive oxygen species
The authors thank Carroll McBride and Kimberly Wix for their expert technical assistance in this study, and Travis Knuckles, Ph.D., for his help in reviewing this manuscript. This work was supported by the National Institutes of Health/National Institute for Environmental Health Sciences [grant numbers R01-ES015022 and RC1 ES018274 (to TRN)].
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.
- 5.Ferrari, R., Ceconi, C., Curello, S., Guarnieri, C., Caldarera, C. M., Albertini, A., et al. (1985). Oxygen-mediated myocardial damage during ischaemia and reperfusion: Role of the cellular defences against oxygen toxicity. Journal of Molecular and Cellular Cardiology, 17, 937–945.CrossRefPubMedGoogle Scholar
- 6.Grech, E. D., Dodd, N. J., Jackson, M. J., Morrison, W. L., Faragher, E. B., & Ramsdale, D. R. (1996). Evidence for free radical generation after primary percutaneous transluminal coronary angioplasty recanalization in acute myocardial infarction. American Journal of Cardiology, 77, 122–127.CrossRefPubMedGoogle Scholar
- 16.Wang, P., Chen, H., Qin, H., Sankarapandi, S., Becher, M. W., Wong, P. C., et al. (1998). Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents postischemic injury. Proceedings of the National Academy of Sciences of the United States of America, 95, 4556–4560.CrossRefPubMedGoogle Scholar
- 29.Nurkiewicz, T. R., & Boegehold, M. A. (2007). High salt intake reduces endothelium-dependent dilation of mouse arterioles via superoxide anion generated from nitric oxide synthase. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 292, R1550–R1556.PubMedGoogle Scholar
- 31.Wang, T., Chiang, E.T., Moreno-Vinasco, L., Lang, G.D., Pendyala, S., Samet, J.M., et al. (2009). Particulate matter disrupts human lung endothelial barrier integrity via ROS- and p38 MAPK-dependent pathways. American Journal of Respiratory Cell and Molecular Biology. [Epub ahead of print] PMID: 19520919.Google Scholar
- 32.Li, Z., Hyseni, X., Carter, J. D., Soukup, J. M., Dailey, L. A., & Huang, Y. C. (2006). Pollutant particles enhanced H2O2 production from NAD(P)H oxidase and mitochondria in human pulmonary artery endothelial cells. American Journal of Physiology. Cell Physiology, 291, C357–C365.CrossRefPubMedGoogle Scholar
- 36.Miller, M. R., Borthwick, S. J., Shaw, C. A., McLean, S. G., McClure, D., Mills, N. L., et al. (2009). Direct impairment of vascular function by diesel exhaust particulate through reduced bioavailability of endothelium-derived nitric oxide induced by superoxide free radicals. Environmental Health Perspectives, 117, 611–616.PubMedGoogle Scholar
- 37.Lund, A. K., Lucero, J., Lucas, S., Madden, M. C., McDonald, J. D., Seagrave, J. C., et al. (2009). Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1-mediated pathways. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 511–517.CrossRefPubMedGoogle Scholar
- 38.Courtois, A., Andujar, P., Ladeiro, Y., Baudrimont, I., Delannoy, E., Leblais, V., et al. (2008). Impairment of NO-dependent relaxation in intralobar pulmonary arteries: Comparison of urban particulate matter and manufactured nanoparticles. Environmental Health Perspectives, 116, 1294–1299.PubMedCrossRefGoogle Scholar
- 39.Cherng, T. W., Campen, M. J., Knuckles, T. L., Gonzalez Bosc, L., & Kanagy, N. L. (2009). Impairment of coronary endothelial cell ET(B) receptor function after short-term inhalation exposure to whole diesel emissions. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 297(3):R640–R647.Google Scholar
- 40.Sherratt, A. J., Culpepper, B. T., & Lubawy, W. C. (1988). Relative participation of the gas phase and total particulate matter in the imbalance in prostacyclin and thromboxane formation seen following chronic cigarette smoke exposure. Prostaglandins Leukotrienes and Essential Fatty Acids, 34, 15–18.CrossRefGoogle Scholar