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Sci Rep. 2019 Mar 6;9(1):3641. doi: 10.1038/s41598-019-40343-w.

Ultrafine particles and ozone perturb norepinephrine clearance rather than centrally generated sympathetic activity in humans.

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Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147, Cologne, Germany.
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 30625, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, 30625, Hannover, Germany.
MHH CRC Core Facility & Centre for Pharmacology and Toxicology, Hannover Medical School, 30625, Hannover, Germany.
Institute for Clinical Pharmacology, Hannover Medical School, 30625, Hannover, Germany.
Kaufmännische Krankenkasse - KKH, Karl-Wiechert-Allee 61, 30625, Hannover, Germany.
Department of Medicine, Division of Clinical Pharmacology, Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Institute of Biostatistics, Hannover Medical School, 30625, Hannover, Germany.
Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, 3015 GE, Rotterdam, The Netherlands.
Department of Laboratory Medicine, Radboud University Medical Centre, 6500 HB, Nijmegen, The Netherlands.
Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147, Cologne, Germany.
Department of Respiratory Medicine, Hannover Medical School, 30625, Hannover, Germany.


Cardiovascular risk rapidly increased following exposure to air pollution. Changes in human autonomic regulation have been implicated based on epidemiological associations between exposure estimates and indirect autonomic nervous system measurements. We conducted a mechanistic study to test the hypothesis that, in healthy older individuals, well-defined experimental exposure to ultrafine carbon particles (UFP) increases sympathetic nervous system activity and more so with added ozone (O3). Eighteen participants (age >50 years, 6 women) were exposed to filtered air (Air), UFP, and UFP + O3 combination for 3 hours during intermittent bicycle ergometer training in a randomized, crossover, double-blind fashion. Two hours following exposure, respiration, electrocardiogram, blood pressure, and muscle sympathetic nerve activity (MSNA) were recorded at supine rest, during deep breathing, and during a Valsalva manoeuvre. Catechols and inflammatory marker levels were measured in venous blood samples. Induced sputum was obtained 3.5 h after exposure. Combined exposure to UFP + O3 but not UFP alone, caused a significant increase in sputum neutrophils and circulating leucocytes. Norepinephrine was modestly increased while the ratio between plasma dihydroxyphenylglycol (DHPG) and norepinephrine levels, a marker for norepinephrine clearance, was reduced with UFP + O3. Resting MSNA was not different (47 ± 12 with Air, 47 ± 14 with UFP, and 45 ± 14 bursts/min with UFP + O3). Indices of parasympathetic heart rate control were unaffected by experimental air pollution. Our study suggests that combined exposure to modest UFP and O3 levels increases peripheral norepinephrine availability through decreased clearance rather than changes in central autonomic activity. Pulmonary inflammatory response may have perturbed pulmonary endothelial norepinephrine clearance.

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