title: Vascular oxidative stress induced by diesel exhaust microparticles:  synergism with hypertension.
abstract: BACKGROUND
  Epidemiological and clinical studies have shown that traffic-related air pollution and, particularly, diesel exhaust particles (DEP) are strongly linked to cardiovascular mortality.
  
  
  METHODS
  Vascular toxicity was studied by assessing vasomotor responses of aortas isolated from normotensive Wistar rats exposed in vitro to DEP (DEP suspension and aqueous DEP extract). In vivo experiments were performed on Wistar rats and spontaneously hypertensive rats (SHRs) exposed for 4 weeks via intratracheal instillation to either DEP or saline vehicle. After killing, vascular responses to acetylcholine (ACh) or sodium nitroprusside were assessed in vitro and the expression of p22phox, a major nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit, was studied by real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  In aortas from Wistar rats, in vitro DEP incubation (both preparations) markedly inhibited the relaxations to ACh and slightly to sodium nitroprusside; this effect was reversed in the presence of superoxide dismutase. In contrast, in aortas from in vivo-exposed animals, ACh-induced relaxations were only significantly impaired in the SHR group, accompanied with a significant upregulation of p22phox and no change in systolic blood pressure.
  
  
  CONCLUSIONS
  Although in vitro exposure to DEP produces a vascular oxidative stress, repeated in vivo exposures to DEP only impair vascular function in SHR, via an upregulation of p22phox. This suggests a synergistic effect on endothelial dysfunction between particulate air pollution and hypertension.
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Pharmacy, Université Libre de Bruxelles, Bruxelles, Belgium. Nathalie.Labranche@ulb.ac.be
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labranche
authors.forename: Charaf
authors.initials: C
authors.lastname: El Khattabi
authors.forename: Laurence
authors.initials: L
authors.lastname: Dewachter
authors.forename: Céline
authors.initials: C
authors.lastname: Dreyfuss
authors.forename: Jeanine
authors.initials: J
authors.lastname: Fontaine
authors.forename: Philippe
authors.initials: P
authors.lastname: van de Borne
authors.forename: Guy
authors.initials: G
authors.lastname: Berkenboom
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pochet
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D052638:Particulate Matter; D014665:Vasodilator Agents; D001335:Vehicle Emissions; D019255:NADPH Oxidases; C515768:Cyba protein, rat