doi: 10.1161/CIRCULATIONAHA.105.588962
(Circulation. 2005;112:3930-3936.)
© 2005 American Heart Association, Inc.
Vascular Medicine |
Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis
From the Centre for Cardiovascular Science (N.L.M., S.D.R., N.A.B., D.E.N.), Edinburgh University, Edinburgh, Scotland; the Department of Respiratory Medicine and Allergy (H.T., M.G., A.B., T.S.), Umeå University, Umeå, Sweden; and the Wellcome Trust Clinical Research Facility (K. Darnley) and ELEGI Colt Laboratory (W.M., K. Donaldson), Centre for Inflammation Research, Edinburgh University, Edinburgh, Scotland.
Reprint requests to Dr Nicholas L. Mills, Centre for Cardiovascular Science, University of Edinburgh, Chancellor’s Bldg, Edinburgh, EH16 4SU, UK. E-mail nick.mills{at}ed.ac.uk
Received December 14, 2004; de novo received August 12, 2005; revision received September 14, 2005; accepted October 7, 2005.
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 µg/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 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 (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.
CLINICAL PERSPECTIVE
This article has been cited by other articles:
 |
|
 |
|
  N. L. Mills, G. Oberdorster, and D. E. Newby Reducing Exposure to Airborne Particles: A Novel Strategy to Improve Cardiovascular Health Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 366 - 367. [Full Text] [PDF]
|
|
|
|
|
|
E. V. Brauner, L. Forchhammer, P. Moller, L. Barregard, L. Gunnarsen, A. Afshari, P. Wahlin, M. Glasius, L. O. Dragsted, S. Basu, et al. Indoor Particles Affect Vascular Function in the Aged: An Air Filtration-based Intervention Study Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 419 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. N. Krivoshto, J. R. Richards, T. E. Albertson, and R. W. Derlet The Toxicity of Diesel Exhaust: Implications for Primary Care J Am Board Fam Med, January 1, 2008; 21(1): 55 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Wadsworth Oxidative stress and the endothelium Exp Physiol, January 1, 2008; 93(1): 155 - 157. [Full Text] [PDF]
|
|
|
|
|
|
D. A. McAllister, J. D. Maclay, N. L. Mills, G. Mair, J. Miller, D. Anderson, D. E. Newby, J. T. Murchison, and W. MacNee Arterial Stiffness Is Independently Associated with Emphysema Severity in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1208 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Briet, C. Collin, S. Laurent, A. Tan, M. Azizi, M. Agharazii, X. Jeunemaitre, F. Alhenc-Gelas, and P. Boutouyrie Endothelial Function and Chronic Exposure to Air Pollution in Normal Male Subjects Hypertension, November 1, 2007; 50(5): 970 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Mills, H. Tornqvist, M. C. Gonzalez, E. Vink, S. D. Robinson, S. Soderberg, N. A. Boon, K. Donaldson, T. Sandstrom, A. Blomberg, et al. Ischemic and Thrombotic Effects of Dilute Diesel-Exhaust Inhalation in Men with Coronary Heart Disease N. Engl. J. Med., September 13, 2007; 357(11): 1075 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Kaufman Air Pollution and Mortality: Are We Closer to Understanding the How? Am. J. Respir. Crit. Care Med., August 15, 2007; 176(4): 325 - 326. [Full Text] [PDF]
|
|
|
|
|
|
H. Tornqvist, N. L. Mills, M. Gonzalez, M. R. Miller, S. D. Robinson, I. L. Megson, W. MacNee, K. Donaldson, S. Soderberg, D. E. Newby, et al. Persistent Endothelial Dysfunction in Humans after Diesel Exhaust Inhalation Am. J. Respir. Crit. Care Med., August 15, 2007; 176(4): 395 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Toren, I. A Bergdahl, T. Nilsson, and B. Jarvholm Occupational exposure to particulate air pollution and mortality due to ischaemic heart disease and cerebrovascular disease Occup. Environ. Med., August 1, 2007; 64(8): 515 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hoffmann, S. Moebus, S. Mohlenkamp, A. Stang, N. Lehmann, N. Dragano, A. Schmermund, M. Memmesheimer, K. Mann, R. Erbel, et al. Residential Exposure to Traffic Is Associated With Coronary Atherosclerosis Circulation, July 31, 2007; 116(5): 489 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B-M. Larsson, M. Sehlstedt, J. Grunewald, C. M. Skold, A. Lundin, A. Blomberg, T. Sandstrom, A. Eklund, and M. Svartengren Road tunnel air pollution induces bronchoalveolar inflammation in healthy subjects Eur. Respir. J., April 1, 2007; 29(4): 699 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Peters When a Myocardial Infarction Comes Out of the Not-So-Blue Air Circulation, December 5, 2006; 114(23): 2430 - 2431. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bhatnagar Environmental Cardiology: Studying Mechanistic Links Between Pollution and Heart Disease Circ. Res., September 29, 2006; 99(7): 692 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Brook, M. S. O'Neill, and S. Rajagopalan Letter by Brook et al Regarding Article "Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis" Circulation, June 20, 2006; 113(24): e871 - e871. [Full Text] [PDF]
|
|
|
|
|
|
N. L. Mills, S. D. Robinson, N. A. Boon, D. E. Newby, H. Tornqvist, M. Gonzalez, A. Blomberg, T. Sandstrom, K. Darnley, W. MacNee, et al. Response to Letter Regarding Article "Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis" Circulation, June 20, 2006; 113(24): e872 - e872. [Full Text] [PDF]
|
|