Persistent endothelial dysfunction in humans after diesel exhaust inhalation

Am J Respir Crit Care Med. 2007 Aug 15;176(4):395-400. doi: 10.1164/rccm.200606-872OC. Epub 2007 Apr 19.

Abstract

Rationale: 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.

Objectives: 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.

Measurements and main 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Acetylcholine / blood
  • Adolescent
  • Adult
  • Antioxidants / analysis
  • Biomarkers / blood
  • Bradykinin / administration & dosage
  • Bradykinin / blood
  • Cross-Over Studies
  • Double-Blind Method
  • Endothelium, Vascular / physiopathology*
  • Environmental Exposure / adverse effects*
  • Forearm / blood supply
  • Humans
  • Inflammation / physiopathology
  • Interleukin-6 / blood
  • Male
  • Nitroprusside / administration & dosage
  • Nitroprusside / analysis
  • P-Selectin / blood
  • Regional Blood Flow / physiology
  • Tumor Necrosis Factor-alpha / blood
  • Vasodilation / physiology
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / blood
  • Vehicle Emissions*
  • Verapamil / administration & dosage
  • Verapamil / blood

Substances

  • Antioxidants
  • Biomarkers
  • Interleukin-6
  • P-Selectin
  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • Vehicle Emissions
  • Nitroprusside
  • Verapamil
  • Acetylcholine
  • Bradykinin