Journal Article

Persistent Endothelial Dysfunction in Humans after Diesel Exhaust Inhalation

MacNee, William, Tornqvist, Hakan, Robinson, Simon D, Sandstrom, Thomas, Megson, Ian L, Mills, Nicholas L, Soderberg, Stefan, Gonzalez, Manuel, Miller, Mark R, Donaldson, Ken, Newby, David E, Blomberg, Anders

2007

Overview

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

• Publisher: Am Thoracic Soc,American Lung Association,Oxford University Press
• Subject: Acetylcholine - administration & dosage / Acetylcholine - blood / Acetylcholine/administration & dosage/blood / Adolescent / Adult / Air pollution / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Antioxidants - analysis / Bats / Biological and medical sciences / Biological Markers/blood / Biomarkers - blood / Blood coagulation. Blood cells / Blood pressure / Blood vessels and receptors / Bradykinin - administration & dosage / Bradykinin - blood / Bradykinin/administration & dosage/blood / Cross-Over Studies / Cytokines / Double-Blind Method / Endothelium / Endothelium, Vascular - physiopathology / Environmental Exposure - adverse effects / Forearm - blood supply / Fundamental and applied biological sciences. Psychology / General aspects, investigation methods, hemostasis, fibrinolysis / Heart attacks / Humans / Inflammation / Inflammation - physiopathology / Intensive care medicine / Interleukin-6 - blood / Investigations / Kinases / Male / Medical sciences / Molecular and cellular biology / Mortality / Nitroprusside - administration & dosage / Nitroprusside - analysis / Nitroprusside/administration & dosage/analysis / Oxidative stress / P-Selectin - blood / Plasma / Pollutants / Regional Blood Flow - physiology / Tumor Necrosis Factor-alpha - blood / Tumor necrosis factor-TNF / Vasodilation - physiology / Vasodilator Agents - administration & dosage / Vasodilator Agents - blood / Vasodilator Agents/administration & dosage/blood / Vehicle Emissions / Verapamil - administration & dosage / Verapamil - blood / Verapamil/administration & dosage/blood / Vertebrates: cardiovascular system