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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
Environmental Health Perspectives
Publication Date
DOI: 10.1289/ehp.0800235
  • Research
  • Medicine


Background Diesel exhaust particulate (DEP) is a key arbiter of the adverse cardiovascular effects of air pollution. Objectives We assessed the in vitro effects of DEP on vascular function, nitric oxide (NO) availability, and the generation of oxygen-centered free radicals. Methods We assessed the direct vascular effects of DEP (10–100 μg/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. Results Acetylcholine-induced relaxation was attenuated by DEP (maximum relaxation reduced from 91 ± 4% to 49 ± 6% with 100 μg/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 μg/mL, DEP did not affect verapamil-induced relaxation (p = 0.73), but at 100 μg/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 μM) were reduced by DEP (100 μg/mL; from 5.2 ± 0.4 to 3.3 ± 0.4 μM; p = 0.002). Free radical generation was increased by DEP (10 μg/mL; 9-fold increase in EPR spectra; p = 0.004) in a manner that could be attenuated by SOD (p = 0.015). Conclusions 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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