title: Diesel exhaust particles induce endothelial dysfunction in apoE-/- mice.
abstract: 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.
  
  
  OBJECTIVE
  We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE(-/-) mice with slight atherosclerosis and from normal apoE(+/+) 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 microg 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(-/-) mice, whereas the response was enhanced in apoE(+/+) mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K(+) or phenylephrine. In vitro exposure to 100 microg DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental and Occupational Health, Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5, Building 5B, 2nd Floor, 1014 Copenhagen K, Denmark.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Hansen
authors.forename: Majid
authors.initials: M
authors.lastname: Sheykhzade
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Janne Kjaergaard
authors.initials: JK
authors.lastname: Folkmann
authors.forename: Ole
authors.initials: O
authors.lastname: Amtorp
authors.forename: Thomas
authors.initials: T
authors.lastname: Jonassen
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009213:Myography; D014665:Vasodilator Agents / Q000494:pharmacology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001057:Apolipoproteins E; D014665:Vasodilator Agents; D001335:Vehicle Emissions; D000109:Acetylcholine