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Exposure to nitrogen dioxide is not associated with vascular dysfunction in man
Centre for Cardiovascular Sciences, University of Edinburgh, United Kingdom.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
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2010 (English)In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 22, no 3, 192-198 p.Article in journal (Refereed) Published
Abstract [en]

Background: Exposure to air pollution is associated with increased cardiorespiratory morbidity and mortality. It is unclear whether these effects are mediated through combustion-derived particulate matter or gaseous components, such as nitrogen dioxide.

Objectives: To investigate the effect of nitrogen dioxide exposure on vascular vasomotor and six fibrinolytic functions.

Methods: Ten healthy male volunteers were exposed to nitrogen dioxide at 4 ppm or filtered air for 1 h during intermittent exercise in a randomized double-blind crossover study. Bilateral forearm blood flow and fibrinolytic markers were measured before and during unilateral intrabrachial infusion of bradykinin (100–1000 pmol/min), acetylcholine (5–20 μg/min), sodium nitroprusside (2–8 μg/min), and verapamil (10–100 μg/min) 4 h after the exposure. Lung function was determined before and after the exposure, and exhaled nitric oxide at baseline and 1 and 4 h after the exposure.

Results: There were no differences in resting forearm blood flow after either exposure. There was a dose-dependent increase in forearm blood flow with all vasodilators but this was similar after either exposure for all vasodilators (p > .05 for all). Bradykinin caused a dose-dependent increase in plasma tissue-plasminogen activator, but again there was no difference between the exposures. There were no changes in lung function or exhaled nitric oxide following either exposure.

Conclusion: Inhalation of nitrogen dioxide does not impair vascular vasomotor or fibrinolytic function. Nitrogen dioxide does not appear to be a major arbiter of the adverse cardiovascular effects of air pollution.

Place, publisher, year, edition, pages
Informa Healthcare, 2010. Vol. 22, no 3, 192-198 p.
Keyword [en]
Air pollution, endothelial function, fibrinolysis, nitrogen dioxide, NO2
National Category
Respiratory Medicine and Allergy
URN: urn:nbn:se:umu:diva-27796DOI: 10.3109/08958370903144105ISI: 000275067200002OAI: diva2:277751
Available from: 2009-11-23 Created: 2009-11-20 Last updated: 2012-02-29Bibliographically approved
In thesis
1. Cardiovascular effects of diesel exhaust: mechanistic and interventional studies
Open this publication in new window or tab >>Cardiovascular effects of diesel exhaust: mechanistic and interventional studies
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Air pollution is associated with negative health effects. Exposure to combustion-derived particulate matter (PM) air pollution has been related to increased incidence of cardiovascular and respiratory morbidity and mortality, specifically in susceptible populations. Ambient particles, with a diameter of less than 2.5 mm, have been suggested to be the strongest contributor to these health effects. Diesel exhaust (DE) is a major source of small combustion-derived PM air pollution world wide. 

In healthy volunteers, exposure to DE, has been associated with airway inflammation and impaired vasomotor function and endogenous fibrinolysis.

The aims of this thesis were to further elucidate the underlying mechanisms to the reported cardiovascular effects following exposure to DE, with specific focus on endothelin-1 (ET-1). Additionally, the vascular effects of the major gaseous component of DE, nitrogen dioxide (NO2), were assessed together with the impact of an exhaust particle trap to reduce the observed negative vascular effects after DE exposure.

Methods: In all studies healthy, non-smoking male volunteers were included and exposed for one hour during intermittent exercise in a randomised double-blind crossover fashion. In studies I-III, subjects were exposed to DE at a particulate matter concentration of approximately 300 μg/m3 and filtered air, on two different occasions. In study V an additional exposure was employed, during which DE was filtered through an exhaust particle trap. In study IV subjects were exposed to nitrogen dioxide (NO2) at 4 ppm or filtered air.

In study I, thrombus formation and platelet activation were assessed using the Badimon ex vivo perfusion chamber and flow cytometry. Study II comprised the determination of arterial stiffness including pulse wave analysis and velocity.

In studies III-V, vascular assessment was performed using venous occlusion plethysmography. In studies IV and V, the vascular responses to intra-arterially infused endothelial-dependent and endothelial-independent vasodilatators were registered. In study III, vascular responses to intra-arterial infusion of Endothelin-1 (ET-1) and ET-1-receptor antagonists were assessed. Venous occlusion phlethysmography was in all cases performed 4-6 hours following exposures. Blood samples for markers of inflammation, coagulation and platelet activation were collected before and throughout the study periods in studies III and V.

Results: Exposure to DE increased ex vivo thrombus formation and arterial stiffness, in terms of augmentation index. DE inhalation impaired vasomotor function and endogenous fibrinolysis. The exhaust particle trap reduced the particle concentration by 98% and abolished the effects on vasomotor function, endogenous fibrinolysis and ex vivo thrombus formation. Plasma concentrations of ET-1 and its precursor big-ET-1 were unchanged following exposure. Dual endothelial receptor antagonism caused similar vasodilatation after both exposures, although vasodilatation to the endothelin-A receptor alone was blunted after DE exposure. ET-1 infusion induced vasoconstriction only following DE exposure. Exposure to nitrogen dioxide did not affect vascular function.

Conclusion: Inhalation of diesel exhaust in young healthy men impaired important and complementary aspects of vascular function in humans; regulation of vascular tone and endogenous fibrinolysis as well as increased ex vivo thrombus formation. The use of an exhaust particle trap significantly reduced particle emissions and abolished the DE-induced vascular and prothrombotic effects. The adverse vascular effects following DE exposure do not appear to be directly mediated through the endothelin system. Neither is NO2 suggested to be a major arbiter of the DE-induced cardiovascular responses. Arterial stiffness is a non-invasive and easily accessible method and could thus be employed to address vascular function in larger field studies. Taken together, this thesis has given further knowledge about the mechanisms underlying the DE-induced vascular effects.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2009. 73 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1317
air pollution, diesel exhaust, nitrogen dioxide, endothelin-1, cardiovascular effects, exhaust particle trap
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
urn:nbn:se:umu:diva-27783 (URN)978-91-7264-868-5 (ISBN)
Public defence
2009-12-11, Sal E04, byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2009-11-23 Created: 2009-11-19 Last updated: 2012-02-22Bibliographically approved

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