title: Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions.
abstract: BACKGROUND
  Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.
  
  
  OBJECTIVE
  To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.
  
  
  METHODS
  In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 microg/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.
  
  
  RESULTS
  Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).
  
  
  CONCLUSIONS
  Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Barath
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
authors.forename: Magnus
authors.initials: M
authors.lastname: Lundbäck
authors.forename: Håkan
authors.initials: H
authors.lastname: Törnqvist
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lucking
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Langrish
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderberg
authors.forename: Christoffer
authors.initials: C
authors.lastname: Boman
authors.forename: Roger
authors.initials: R
authors.lastname: Westerholm
authors.forename: Jakob
authors.initials: J
authors.lastname: Löndahl
authors.forename: Ken
authors.initials: K
authors.lastname: Donaldson
authors.forename: Ian S
authors.initials: IS
authors.lastname: Mudway
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandström
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; D001335:Vehicle Emissions