Cardiovascular effects of exposure to diesel exhaust: mechanistic and interventional studies

摘要: Air pollution is associated with negative health effects. Exposure to combustion-derived particulate matter (PM) air has been related increased incidence of cardiovascular and respiratory morbidity mortality, specifically in susceptible populations. Ambient particles, a diameter less than 2.5 mm, have suggested be the strongest contributor these Diesel exhaust (DE) major source small PM world wide. In healthy volunteers, exposure DE, airway inflammation impaired vasomotor function endogenous fibrinolysis. The aims this thesis were further elucidate underlying mechanisms reported effects following specific focus on endothelin-1 (ET-1). Additionally, vascular gaseous component nitrogen dioxide (NO2), assessed together impact an particle trap reduce observed after DE exposure. Methods: all studies healthy, non-smoking male volunteers included exposed for one hour during intermittent exercise randomised double-blind crossover fashion. I-III, subjects at concentration approximately 300 microgram/m3 filtered air, two different occasions. study V additional was employed, which through trap. IV (NO2) 4 ppm or air. I, thrombus formation platelet activation using Badimon ex vivo perfusion chamber flow cytometry. Study II comprised determination arterial stiffness including pulse wave analysis velocity. III-V, assessment performed venous occlusion plethysmography. V, responses intra-arterially infused endothelial-dependent endothelial-independent vasodilatators registered. III, intra-arterial infusion Endothelin-1 (ET-1) ET-1-receptor antagonists assessed. Venous phlethysmography cases 4-6 hours exposures. Blood samples markers inflammation, coagulation collected before throughout periods III V. Results: stiffness, terms augmentation index. inhalation reduced by 98 per cent abolished function, fibrinolysis formation. Plasma concentrations ET-1 its precursor big-ET-1 unchanged Dual endothelial receptor antagonism caused similar vasodilatation both exposures, although endothelin-A alone blunted induced vasoconstriction only did not affect function. Conclusion: Inhalation diesel young men important complementary aspects humans; regulation tone as well use significantly emissions DE-induced prothrombotic adverse do appear directly mediated endothelin system. Neither NO2 arbiter responses. Arterial non-invasive easily accessible method could thus employed address larger field studies. Taken together, given knowledge about (A). http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-27783.