Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.
BACKGROUND
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.


RESULTS
In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 microg/m3 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 microg/min), sodium nitroprusside (2 to 8 microg/min), and verapamil (10 to 100 microg/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 (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<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 (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%).


CONCLUSIONS
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.
Mills
Nicholas L
NL
Centre for Cardiovascular Science, Edinburgh University, Edinburgh, Scotland. nick.mills@ed.ac.uk
Törnqvist
Håkan
H
Robinson
Simon D
SD
Gonzalez
Manuel
M
Darnley
Kareen
K
MacNee
William
W
Boon
Nicholas A
NA
Donaldson
Ken
K
Blomberg
Anders
A
Sandstrom
Thomas
T
Newby
David E
DE
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004781:Environmental Exposure / Q000009:adverse effects; D005080:Exercise Test; D005342:Fibrinolysis; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007249:Inflammation; D001239:Inhalation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology; D001335:Vehicle Emissions / Q000633:toxicity*
D014665:Vasodilator Agents; D001335:Vehicle Emissions; D010959:Tissue Plasminogen Activator