title: Persistent endothelial dysfunction in humans after diesel exhaust inhalation.
abstract: BACKGROUND
  Exposure to combustion-derived air pollution is associated with an early (1-2 h) and sustained (24 h) rise in cardiovascular morbidity and mortality. We have previously demonstrated that inhalation of diesel exhaust causes an immediate (within 2 h) impairment of vascular and endothelial function in humans.
  
  
  OBJECTIVE
  To investigate the vascular and systemic effects of diesel exhaust in humans 24 hours after inhalation.
  
  
  METHODS
  Fifteen healthy men were exposed to diesel exhaust (particulate concentration, 300 microg/m(3)) or filtered air for 1 hour in a double-blind, randomized, crossover study. Twenty-four hours after exposure, bilateral forearm blood flow, and inflammatory and fibrinolytic markers were measured before and during unilateral intrabrachial bradykinin (100-1,000 pmol/min), acetylcholine (5-20 microg/min), sodium nitroprusside (2-8 microg/min), and verapamil (10-100 microg/min) infusions.
  
  
  RESULTS
  Resting forearm blood flow, blood pressure, and basal fibrinolytic markers were similar 24 hours after either exposure. Diesel exhaust increased plasma cytokine concentrations (tumor necrosis factor-alpha and interleukin-6, p < 0.05 for both) but appeared to reduce acetylcholine (p = 0.01), and bradykinin (p = 0.08) induced forearm vasodilatation. In contrast, there were no differences in either endothelium-independent (sodium nitroprusside and verapamil) vasodilatation or bradykinin-induced acute plasma tissue plasminogen activator release.
  
  
  CONCLUSIONS
  Twenty-four hours after diesel exposure, there is a selective and persistent impairment of endothelium-dependent vasodilatation that occurs in the presence of mild systemic inflammation. These findings suggest that combustion-derived air pollution may have important systemic and adverse vascular effects for at least 24 hours after exposure.
authors: Department of Respiratory Medicine and Allergy, Umeå University Hospital, SE-901 85 Umeå, Sweden.
authors: Håkan
authors: H
authors: Törnqvist
authors: Nicholas L
authors: NL
authors: Mills
authors: Manuel
authors: M
authors: Gonzalez
authors: Mark R
authors: MR
authors: Miller
authors: Simon D
authors: SD
authors: Robinson
authors: Ian L
authors: IL
authors: Megson
authors: William
authors: W
authors: Macnee
authors: Ken
authors: K
authors: Donaldson
authors: Stefan
authors: S
authors: Söderberg
authors: David E
authors: DE
authors: Newby
authors: Thomas
authors: T
authors: Sandström
authors: Anders
authors: A
authors: Blomberg
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000097:blood; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001920:Bradykinin / Q000008:administration & dosage / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004781:Environmental Exposure / Q000009:adverse effects*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage / Q000032:analysis; D019007:P-Selectin / Q000097:blood; D012039:Regional Blood Flow / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood; D001335:Vehicle Emissions; D014700:Verapamil / Q000008:administration & dosage / Q000097:blood
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D015850:Interleukin-6; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D001335:Vehicle Emissions; D009599:Nitroprusside; D014700:Verapamil; D000109:Acetylcholine; D001920:Bradykinin