Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis

被引:491
作者
Mills, NL
Törnqvist, H
Robinson, SD
Gonzalez, M
Darnley, K
MacNee, W
Boon, NA
Donaldson, K
Blomberg, A
Sandstrom, T
Newby, DE
机构
[1] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh EH16 4SU, Midlothian, Scotland
[2] Umea Univ, Dept Resp Med & Allergy, Umea, Sweden
[3] Univ Edinburgh, Ctr Inflammat Res, Wellcome Trust Clin Res Facil, Edinburgh, Midlothian, Scotland
[4] Univ Edinburgh, Ctr Inflammat Res, ELEGI Colt Lab, Edinburgh, Midlothian, Scotland
关键词
air pollution; endothelium; blood flow; fibrinolysis;
D O I
10.1161/CIRCULATIONAHA.105.588962
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. Methods and Results - In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 mu g/m(3) 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 mu g/min), sodium nitroprusside (2 to 8 mu g/min), and verapamil (10 to 100 mu g/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.
引用
收藏
页码:3930 / 3936
页数:7
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