Persistent endothelial dysfunction in humans after diesel exhaust inhalation.
BACKGROUND
Exposure to combustion-derived air pollution is associated with an early (1-2 h) and sustained (24 h) rise in cardiovascular morbidity and mortality. We have previously demonstrated that inhalation of diesel exhaust causes an immediate (within 2 h) impairment of vascular and endothelial function in humans.


OBJECTIVE
To investigate the vascular and systemic effects of diesel exhaust in humans 24 hours after inhalation.


METHODS
Fifteen healthy men were exposed to diesel exhaust (particulate concentration, 300 microg/m(3)) or filtered air for 1 hour in a double-blind, randomized, crossover study. Twenty-four hours after exposure, bilateral forearm blood flow, and inflammatory and fibrinolytic markers were measured before and during unilateral intrabrachial bradykinin (100-1,000 pmol/min), acetylcholine (5-20 microg/min), sodium nitroprusside (2-8 microg/min), and verapamil (10-100 microg/min) infusions.


RESULTS
Resting forearm blood flow, blood pressure, and basal fibrinolytic markers were similar 24 hours after either exposure. Diesel exhaust increased plasma cytokine concentrations (tumor necrosis factor-alpha and interleukin-6, p < 0.05 for both) but appeared to reduce acetylcholine (p = 0.01), and bradykinin (p = 0.08) induced forearm vasodilatation. In contrast, there were no differences in either endothelium-independent (sodium nitroprusside and verapamil) vasodilatation or bradykinin-induced acute plasma tissue plasminogen activator release.


CONCLUSIONS
Twenty-four hours after diesel exposure, there is a selective and persistent impairment of endothelium-dependent vasodilatation that occurs in the presence of mild systemic inflammation. These findings suggest that combustion-derived air pollution may have important systemic and adverse vascular effects for at least 24 hours after exposure.
Törnqvist
Håkan
H
Department of Respiratory Medicine and Allergy, Umeå University Hospital, SE-901 85 Umeå, Sweden.
Mills
Nicholas L
NL
Gonzalez
Manuel
M
Miller
Mark R
MR
Robinson
Simon D
SD
Megson
Ian L
IL
Macnee
William
W
Donaldson
Ken
K
Söderberg
Stefan
S
Newby
David E
DE
Sandström
Thomas
T
Blomberg
Anders
A
D000109:Acetylcholine / Q000008:administration & dosage / Q000097:blood; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001920:Bradykinin / Q000008:administration & dosage / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004781:Environmental Exposure / Q000009:adverse effects*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage / Q000032:analysis; D019007:P-Selectin / Q000097:blood; D012039:Regional Blood Flow / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood; D001335:Vehicle Emissions; D014700:Verapamil / Q000008:administration & dosage / Q000097:blood
D000975:Antioxidants; D015415:Biomarkers; D015850:Interleukin-6; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D001335:Vehicle Emissions; D009599:Nitroprusside; D014700:Verapamil; D000109:Acetylcholine; D001920:Bradykinin