Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 μg/m <jats:sup>3</jats:sup> particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 μg/min), sodium nitroprusside (2 to 8 μg/min), and verapamil (10 to 100 μg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator ( <jats:italic>P</jats:italic> <0.0001 for all), this response was attenuated with bradykinin ( <jats:italic>P</jats:italic> <0.05), acetylcholine ( <jats:italic>P</jats:italic> <0.05), and sodium nitroprusside ( <jats:italic>P</jats:italic> <0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator ( <jats:italic>P</jats:italic> <0.0001) that was suppressed 6 hours after exposure to diesel ( <jats:italic>P</jats:italic> <0.001; area under the curve decreased by 34%). </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction. </jats:p>