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Title: Diesel exhaust particles induce endothelial dysfunction in apoE{sup -/-} mice

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [2];  [1];  [1];  [3];  [3];  [1]
  1. Department of Environmental and Occupational Health, Institute of Public Health, University of Copenhagen, Oster Farimagsgade 5, Building 5B, 2nd Floor, 1014 Copenhagen K (Denmark)
  2. Department of Pharmacology and Pharmacotherapy, Danish University of Pharmaceutical Sciences (Denmark)
  3. Department of Pharmacology, University of Copenhagen (Denmark)

Background: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function, possibly dependent on present atherosclerosis. Aim: We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE{sup -/-} mice with slight atherosclerosis and from normal apoE{sup +/+} mice. Methods: DEP 0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were sacrificed 1 h later and aorta ring segments were mounted on wire myographs. Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100 {mu}g DEP/ml before measurement of vasomotor functions. Results: Exposure to 0.5 mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine elicited vasorelaxation in apoE{sup -/-} mice, whereas the response was enhanced in apoE{sup +/+} mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K{sup +} or phenylephrine. In vitro exposure to 100 {mu}g DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure. Conclusion: Exposure to DEP has acute effect on vascular functions. Endothelial dysfunction possibly due to decreased NO production as suggested by decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside response can be induced by DEP in vivo only in vessels of mice with some atherosclerosis.

OSTI ID:
20976866
Journal Information:
Toxicology and Applied Pharmacology, Vol. 219, Issue 1; Other Information: DOI: 10.1016/j.taap.2006.10.032; PII: S0041-008X(06)00402-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
Country of Publication:
United States
Language:
English