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TitleDirect impairment of vascular function by diesel exhaust particulate through reduced bioavailability of endothelium-derived nitric oxide induced by superoxide free radicals
Publication TypeJournal Article
Year of Publication2009
AuthorsMiller, M. R., Borthwick S. J., Shaw C. A., McLean S. G., McClure D., Mills N. L., Duffin R., Donaldson K., Megson I. L., Hadoke P. W. F., & Newby D. E.
JournalEnvironmental Health Perspectives
Pagination611 - 616
Date Published2009/04//
ISBN Number1552-9924
KeywordsAir Pollutants, Animals, Endothelium, Vascular, Free Radical Scavengers, Male, Nitric Oxide, Oxidative Stress, Particulate Matter, Rats, Rats, Wistar, Superoxide Dismutase, Superoxides, Vasodilation, Vehicle Emissions

Diesel exhaust particulate (DEP) is a key arbiter of the adverse cardiovascular effects of air pollution.We assessed the in vitro effects of DEP on vascular function, nitric oxide (NO) availability, and the generation of oxygen-centered free radicals.
We assessed the direct vascular effects of DEP (10-100 microg/mL) in isolated rat aortic rings using myography. We investigated NO scavenging and oxygen-centered free radical generation using an NO electrode and electron paramagnetic resonance (EPR) with the Tempone-H (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) spin trap, respectively.
Acetylcholine-induced relaxation was attenuated by DEP (maximum relaxation reduced from 91 +/- 4% to 49 +/- 6% with 100 microg/mL DEP; p < 0.001) but was restored by superoxide dismutase (SOD; maximum relaxation, 73 +/- 6%; p < 0.001). DEP caused a modest inhibition of relaxation to NO donor drugs, an effect that could be reversed by SOD (p < 0.01). At 10 microg/mL, DEP did not affect verapamil-induced relaxation (p = 0.73), but at 100 microg/mL DEP inhibited relaxation (p < 0.001) by a mechanism independent of SOD. NO concentrations generated by 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO; 10 microM) were reduced by DEP (100 microg/mL; from 5.2 +/- 0.4 to 3.3 +/- 0.4 microM; p = 0.002). Free radical generation was increased by DEP (10 microg/mL; 9-fold increase in EPR spectra; p = 0.004) in a manner that could be attenuated by SOD (p = 0.015).
DEP caused oxidative stress through the generation of oxygen-centered free radicals that reduced the bioavailability of endothelium-derived NO without prior interaction with the lung or vascular tissue. These findings provide a mechanism for the adverse cardiovascular effects of particulate air pollution.


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