title: Pretreatment with Antioxidants Augments the Acute Arterial Vasoconstriction Caused by Diesel Exhaust Inhalation.
abstract: Diesel exhaust inhalation, which is the model traffic-related air pollutant exposure, is associated with vascular dysfunction.
  
  
  
  To determine whether healthy subjects exposed to diesel exhaust exhibit acute vasoconstriction and whether this effect could be modified by the use of antioxidants or by common variants in the angiotensin II type 1 receptor (AGTR1) and other candidate genes.
  
  
  
  In a genotype-stratified, double-blind, four-way crossover study, 21 healthy adult subjects were exposed at rest in a randomized, balanced order to diesel exhaust (200 μg/m(3) particulate matter with an aerodynamic diameter ≤ 2.5 μm [PM2.5]) and filtered air, and to pretreatment with antioxidants (N-acetylcysteine and ascorbate) and placebo. Before and after each exposure, brachial artery diameter (BAd) was assessed using ultrasound. Changes in BAd were compared across pretreatment and exposure sessions. Gene-exposure interactions were evaluated in the AGTR1 A1166C polymorphism, on which recruitment was stratified, and other candidate genes, including TRPV1 and GSTM1.
  
  
  
  Compared with filtered air, exposure to diesel exhaust resulted in a significant reduction in BAd (mean, -0.09 mm, 95% confidence interval [CI], -0.01 to -0.17; P = 0.03). Pretreatment with antioxidants augmented diesel exhaust-related vasoconstriction with a mean change in BAd of -0.18 mm (95% CI, -0.28 to -0.07 mm; P = 0.001). Diesel exhaust-related vasoconstriction was primarily observed in the variant alleles of AGTR1 and TRPV1. No association was found between diesel exhaust inhalation and flow-mediated dilation.
  
  
  
  We confirmed that short-term exposure to diesel exhaust in healthy subjects is associated with acute vasoconstriction in a conductance artery and found suggestive evidence of involvement of nociception and renin-angiotensin systems in this effect. Pretreatment with an antioxidant regimen increased vasoconstriction.
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Cora S
authors.initials: CS
authors.lastname: Sack
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Jansen
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Cosselman
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Trenga
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Pat L
authors.initials: PL
authors.lastname: Stapleton
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Jason
authors.initials: J
authors.lastname: Allen
authors.affiliation: 2 Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Peretz
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Casey
authors.initials: C
authors.lastname: Olives
authors.affiliation: 1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
authors.forename: Joel D
authors.identifier: 0000-0003-4174-9037
authors.initials: JD
authors.lastname: Kaufman
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged; D014463:Ultrasonography; D014661:Vasoconstriction / Q000187:drug effects*; D001335:Vehicle Emissions; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D001335:Vehicle Emissions; D001205:Ascorbic Acid; D000111:Acetylcysteine
keywords: air pollution; antioxidants; cardiovascular physiological processes/drug effects; environmental exposures