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Pulmonary exposure to residual oil fly ash (ROFA) impairs systemic microvascular endothelium-dependent dilation.
Nurkiewicz TR; Boegehold MA; Porter DW; Barger M; Hubbs AF; Millecchia L; Castranova V
Toxicologist 2005 Mar; 84(Suppl 1):294
Epidemiology studies link elevated ambient particulate matter (PM) with increased cardiovascular mortality and morbidity. However, the mechanisms involved are unclear. The present study investigated whether pulmonary exposure to PM could alter systemic microvascular function. Rats were exposed to ROFA (0.1, 0.25, 1, or 2 mg/rat), TiO2 (0.25 mg/rat) or saline by intratracheal instillation. At 24 hr postexposure, bronchoalveolar lavage (BAL) was performed to monitor markers of pulmonary damage and inflammation. Another set of rats was prepared for histopathological analysis. A third set of rats was used for in vivo microscopic analysis of the arterioles of the exteriorized right spinotrapezius muscle, leaving innervation and feed vessels intact. BAL markers of pulmonary damage and inflammation were elevated at 1 and 2 mg/rat ROFA, but not after 0.1 and 0.25 mg/rat ROFA or 0.25 mg/rat TiO2. Histopathology indicated the presence of slight focal inflammation at all PM exposures. In vivo microscopic analysis indicated that ROFA did not affect resting systemic microvascular diameter or tone. However, ROFA significantly inhibited vasodilation in response to lumenally injected Ca2+ ionophore (A23187), with complete inhibition at >/= 0.25 mg/rat ROFA and 65% inhibition at 0.1 mg/rat. The effect of 0.25 mg/rat TiO2 on A23187-induced vasodilation was similar to 0.25 mg/rat ROFA. Pulmonary PM exposure did not affect the responsiveness of arterial smooth muscle to a nitric oxide generator indicating an effect on endothelial cells. In addition, ROFA (2 mg/rat) resulted in systemic inflammation as evidenced by: (1) adherence of PMN to the systemic arterioles, (2) increased FMLP-induced chemiluminescence from isolated blood PMN, and (3) increased dihydroethidium oxidation at the arteriolar wall. These results indicate that pulmonary exposure to ROFA causes systemic inflammation, which compromises the influence of nitric oxide on endothelium-dependent vasodilation.
Epidemiology; Fly-ash; Oils; Exposure-levels; Cardiovascular-system-disorders; Mortality-rates; Mortality-data; Morbidity-rates; Laboratory-animals; Animals; Animal-studies; Histopathology; In-vivo-studies; Microscopic-analysis; Pulmonary-system-disorders; Respiratory-system-disorders; Exposure-assessment; Particulates; Particulate-dust; Aerosol-particles; Aerosols
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division