{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T02:55:20Z","timestamp":1793847320760,"version":"4.6.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 (O<jats:sub>3<\/jats:sub>). Eighteen participants (age &gt;50 years, 6 women) were exposed to filtered air (Air), UFP, and UFP\u2009+\u2009O<jats:sub>3<\/jats:sub> combination for 3\u2009hours 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\u2009h after exposure. Combined exposure to UFP\u2009+\u2009O<jats:sub>3<\/jats:sub> 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\u2009+\u2009O<jats:sub>3<\/jats:sub>. Resting MSNA was not different (47\u2009\u00b1\u200912 with Air, 47\u2009\u00b1\u200914 with UFP, and 45\u2009\u00b1\u200914 bursts\/min with UFP\u2009+\u2009O<jats:sub>3<\/jats:sub>). Indices of parasympathetic heart rate control were unaffected by experimental air pollution. Our study suggests that combined exposure to modest UFP and O<jats:sub>3<\/jats:sub> 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.<\/jats:p>","DOI":"10.1038\/s41598-019-40343-w","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T11:07:05Z","timestamp":1551870425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Ultrafine particles and ozone perturb norepinephrine clearance rather than centrally generated sympathetic activity in humans"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2571-5585","authenticated-orcid":false,"given":"Karsten","family":"Heusser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5672-1187","authenticated-orcid":false,"given":"Jens","family":"Tank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Holz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-4244","authenticated-orcid":false,"given":"Marcus","family":"May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Brinkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Engeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-0294","authenticated-orcid":false,"given":"Andr\u00e9","family":"Diedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodor","family":"Framke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Gro\u00dfhennig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H.","family":"Jan Danser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-3070","authenticated-orcid":false,"given":"Fred C. G. J.","family":"Sweep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Krug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens M.","family":"Hohlfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,6]]},"reference":[{"key":"40343_CR1","unstructured":"World Health Organisation World Health Report: reducing risks and promoting healthy life. (2002)."},{"key":"40343_CR2","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1161\/01.CIR.0000108927.80044.7F","volume":"109","author":"CA Pope III","year":"2004","unstructured":"Pope, C. A. III et al. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation 109, 71\u201377 (2004).","journal-title":"Circulation"},{"key":"40343_CR3","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1161\/01.CIR.103.23.2810","volume":"103","author":"A Peters","year":"2001","unstructured":"Peters, A., Dockery, D. W., Muller, J. E. & Mittleman, M. A. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 103, 2810\u20132815 (2001).","journal-title":"Circulation"},{"key":"40343_CR4","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1093\/aje\/kwi143","volume":"161","author":"DQ Rich","year":"2005","unstructured":"Rich, D. Q. et al. Association of short-term ambient air pollution concentrations and ventricular arrhythmias. Am. J. Epidemiol. 161, 1123\u20131132 (2005).","journal-title":"Am. J. Epidemiol."},{"key":"40343_CR5","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1093\/oxfordjournals.aje.a009934","volume":"150","author":"A Peters","year":"1999","unstructured":"Peters, A. et al. Increases in heart rate during an air pollution episode. Am. J. Epidemiol. 150, 1094\u20131098 (1999).","journal-title":"Am. J. Epidemiol."},{"key":"40343_CR6","doi-asserted-by":"publisher","first-page":"571","DOI":"10.2105\/AJPH.91.9.1346","volume":"91","author":"A Ibald-Mulli","year":"2001","unstructured":"Ibald-Mulli, A., Stieber, J., Wichmann, H. E., Koenig, W. & Peters, A. Effects of air pollution on blood pressure: a population-based approach. Am. J. Public Health 91, 571\u2013577 (2001).","journal-title":"Am. J. Public Health"},{"key":"40343_CR7","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/hc3401.095038","volume":"104","author":"SR Magari","year":"2001","unstructured":"Magari, S. R. et al. Association of heart rate variability with occupational and environmental exposure to particulate air pollution. Circulation. 104, 986\u2013991 (2001).","journal-title":"Circulation."},{"key":"40343_CR8","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1080\/08958370801903800","volume":"20","author":"JM Cavallari","year":"2008","unstructured":"Cavallari, J. M. et al. Time course of heart rate variability decline following particulate matter exposures in an occupational cohort. Inhal. Toxicol. 20, 415\u2013422 (2008).","journal-title":"Inhal. Toxicol."},{"key":"40343_CR9","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1097\/01.jom.0000229781.27181.7d","volume":"48","author":"H Luttmann-Gibson","year":"2006","unstructured":"Luttmann-Gibson, H. et al. Short-term effects of air pollution on heart rate variability in senior adults in Steubenville, Ohio. J. Occup. Environ. Med. 48, 780\u2013788 (2006).","journal-title":"J. Occup. Environ. Med."},{"key":"40343_CR10","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1080\/08958370490439470","volume":"16","author":"H Gong Jr.","year":"2004","unstructured":"Gong, H. Jr. et al. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles. Inhal. Toxicol. 16, 335\u2013343 (2004).","journal-title":"Inhal. Toxicol."},{"key":"40343_CR11","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1253\/circj.72.144","volume":"72","author":"Y Niwa","year":"2008","unstructured":"Niwa, Y., Hiura, Y., Sawamura, H. & Iwai, N. Inhalation exposure to carbon black induces inflammatory response in rats. Circ. J. 72, 144\u2013149 (2008).","journal-title":"Circ. J."},{"key":"40343_CR12","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1161\/ATVBAHA.108.166967","volume":"28","author":"Q Sun","year":"2008","unstructured":"Sun, Q. et al. Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho\/ROCK. Arterioscler. Thromb. Vasc. Biol. 28, 1760\u20131766 (2008).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"40343_CR13","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1161\/CIRCULATIONAHA.116.026796","volume":"136","author":"H Li","year":"2017","unstructured":"Li, H. et al. Particulate matter exposure and stress hormone levels: A randomized, double-blind, crossover trial of air purification. Circulation 136, 618\u2013627 (2017).","journal-title":"Circulation"},{"key":"40343_CR14","doi-asserted-by":"publisher","first-page":"76s","DOI":"10.1183\/09031936.03.00402403","volume":"40","author":"RB Devlin","year":"2003","unstructured":"Devlin, R. B., Ghio, A. J., Kehrl, H., Sanders, G. & Cascio, W. Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability. Eur. Respir. J. Suppl. 40, 76s\u201380s (2003).","journal-title":"Eur. Respir. J. Suppl."},{"key":"40343_CR15","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1161\/01.CIR.101.11.1267","volume":"101","author":"DR Gold","year":"2000","unstructured":"Gold, D. R. et al. Ambient pollution and heart rate variability. Circulation 101, 1267\u20131273 (2000).","journal-title":"Circulation"},{"key":"40343_CR16","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1080\/08958370490439597","volume":"16","author":"G Oberdorster","year":"2004","unstructured":"Oberdorster, G. et al. Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 16, 437\u2013445 (2004).","journal-title":"Inhal. Toxicol."},{"key":"40343_CR17","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1136\/oem.2007.035253","volume":"65","author":"SE Alexeeff","year":"2008","unstructured":"Alexeeff, S. E. et al. Ozone exposure, antioxidant genes, and lung function in an elderly cohort: VA normative aging study. Occup. Environ. Med. 65, 736\u2013742 (2008).","journal-title":"Occup. Environ. Med."},{"key":"40343_CR18","doi-asserted-by":"crossref","unstructured":"Traboulsi, H. et al. Inhaled Pollutants: The molecular scene behind respiratory and systemic diseases associated with ultrafine particulate matter. Int. J. Mol. Sci. 18 (2017).","DOI":"10.3390\/ijms18020243"},{"key":"40343_CR19","unstructured":"Janssen, N.A.H. et al. Health effects of black carbon. 86 (WHO Regional Office for Europe, 2012)."},{"key":"40343_CR20","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1164\/rccm.200611-1627OC","volume":"176","author":"KJ Chuang","year":"2007","unstructured":"Chuang, K. J., Chan, C. C., Su, T. C., Lee, C. T. & Tang, C. S. The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. Am. J. Respir. Crit. Care Med. 176, 370\u2013376 (2007).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"40343_CR21","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1161\/01.CIR.0000013838.94747.64","volume":"105","author":"RD Brook","year":"2002","unstructured":"Brook, R. D. et al. Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation 105, 1534\u20131536 (2002).","journal-title":"Circulation"},{"key":"40343_CR22","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1001\/jama.292.19.2372","volume":"292","author":"ML Bell","year":"2004","unstructured":"Bell, M. L., McDermott, A., Zeger, S. L., Samet, J. M. & Dominici, F. Ozone and short-term mortality in 95 US urban communities, 1987-2000. JAMA 292, 2372\u20132378 (2004).","journal-title":"JAMA"},{"key":"40343_CR23","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1080\/15287399409531838","volume":"41","author":"GJ Jakab","year":"1994","unstructured":"Jakab, G. J. & Hemenway, D. R. Concomitant exposure to carbon black particulates enhances ozone-induced lung inflammation and suppression of alveolar macrophage phagocytosis. J. Toxicol. Environ. Health 41, 221\u2013231 (1994).","journal-title":"J. Toxicol. Environ. Health"},{"key":"40343_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-014-0039-3","volume":"11","author":"F Schaumann","year":"2014","unstructured":"Schaumann, F. et al. Effects of ultrafine particles on the allergic inflammation in the lung of asthmatics: results of a double-blinded randomized cross-over clinical pilot study. Part. Fibre Toxicol. 11, 39 (2014).","journal-title":"Part. Fibre Toxicol."},{"key":"40343_CR25","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1080\/08940630.1989.10466554","volume":"39","author":"M Lippmann","year":"1989","unstructured":"Lippmann, M. Health effects of ozone. A critical review. JAPCA 39, 672\u2013695 (1989).","journal-title":"JAPCA"},{"key":"40343_CR26","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1164\/rccm.200309-1325PP","volume":"169","author":"IS Mudway","year":"2004","unstructured":"Mudway, I. S. & Kelly, F. J. An investigation of inhaled ozone dose and the magnitude of airway inflammation in healthy adults. Am. J. Respir. Crit. Care Med. 169, 1089\u20131095 (2004).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"40343_CR27","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1164\/ajrccm.159.3.9806098","volume":"159","author":"O Holz","year":"1999","unstructured":"Holz, O. et al. Ozone-induced airway inflammatory changes differ between individuals and are reproducible. Am. J. Respir. Crit. Care Med. 159, 776\u2013784 (1999).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"40343_CR28","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1373\/clinchem.2003.023135","volume":"49","author":"JJ Willemsen","year":"2003","unstructured":"Willemsen, J. J., Sweep, C. G., Lenders, J. W. & Ross, H. A. Stability of plasma free metanephrines during collection and storage as assessed by an optimized HPLC method with electrochemical detection. Clin. Chem. 49, 1951\u20131953 (2003).","journal-title":"Clin. Chem."},{"key":"40343_CR29","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1097\/00004872-199816060-00017","volume":"16","author":"AH Danser","year":"1998","unstructured":"Danser, A. H. et al. Determinants of interindividual variation of renin and prorenin concentrations: evidence for a sexual dimorphism of (pro)renin levels in humans. J. Hypertens. 16, 853\u2013862 (1998).","journal-title":"J. Hypertens."},{"key":"40343_CR30","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/j.jchromb.2010.06.022","volume":"879","author":"AA Zoerner","year":"2011","unstructured":"Zoerner, A. A. et al. Unique pentafluorobenzylation and collision-induced dissociation for specific and accurate GC-MS\/MS quantification of the catecholamine metabolite 3,4-dihydroxyphenylglycol (DHPG) in human urine. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 879, 1444\u20131456 (2011).","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"40343_CR31","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s40360-015-0021-1","volume":"16","author":"O Holz","year":"2015","unstructured":"Holz, O. et al. Efficacy and safety of inhaled calcium lactate PUR118 in the ozone challenge model\u2013a clinical trial. BMC Pharmacol. Toxicol. 16, 21 (2015).","journal-title":"BMC Pharmacol. Toxicol."},{"issue":"Suppl","key":"40343_CR32","first-page":"79","volume":"3","author":"G Bertinieri","year":"1985","unstructured":"Bertinieri, G. et al. A new approach to analysis of the arterial baroreflex. J. Hypertens. Suppl. 3(Suppl), 79\u201381 (1985).","journal-title":"J. Hypertens. Suppl."},{"key":"40343_CR33","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/j.1365-2125.1979.tb05903.x","volume":"8","author":"M Hills","year":"1979","unstructured":"Hills, M. & Armitage, P. The two-period cross-over clinical trial. Br. J. Clin. Pharmacol. 8, 7\u201320 (1979).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"40343_CR34","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1016\/j.bbagen.2016.07.015","volume":"1860","author":"PA Bromberg","year":"2016","unstructured":"Bromberg, P. A. Mechanisms of the acute effects of inhaled ozone in humans. Biochim. Biophys. Acta 1860, 2771\u20132781 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"40343_CR35","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1016\/S0735-1097(01)01616-3","volume":"38","author":"S Zevin","year":"2001","unstructured":"Zevin, S., Saunders, S., Gourlay, S. G., Jacob, P. & Benowitz, N. L. Cardiovascular effects of carbon monoxide and cigarette smoking. J. Am. Coll. Cardiol. 38, 1633\u20131638 (2001).","journal-title":"J. Am. Coll. Cardiol."},{"key":"40343_CR36","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1289\/ehp.1002237","volume":"118","author":"JC Stewart","year":"2010","unstructured":"Stewart, J. C. et al. Vascular effects of ultrafine particles in persons with type 2 diabetes. Environ. Health Perspect. 118, 1692\u20131698 (2010).","journal-title":"Environ. Health Perspect."},{"key":"40343_CR37","doi-asserted-by":"publisher","first-page":"e18737","DOI":"10.1371\/journal.pone.0018737","volume":"6","author":"J Tank","year":"2011","unstructured":"Tank, J. et al. Effect of acute ozone induced airway inflammation on human sympathetic nerve traffic: a randomized, placebo controlled, crossover study. PLoS One 6, e18737 (2011).","journal-title":"PLoS One"},{"key":"40343_CR38","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1053\/rmed.2001.1265","volume":"96","author":"N Stenfors","year":"2002","unstructured":"Stenfors, N. et al. Effect of ozone on bronchial mucosal inflammation in asthmatic and healthy subjects. Respir. Med. 96, 352\u2013358 (2002).","journal-title":"Respir. Med."},{"key":"40343_CR39","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1164\/ajrccm\/148.5.1363","volume":"148","author":"RM Aris","year":"1993","unstructured":"Aris, R. M. et al. Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy. Am. Rev. Respir. Dis. 148, 1363\u20131372 (1993).","journal-title":"Am. Rev. Respir. Dis."},{"key":"40343_CR40","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1152\/jappl.1993.74.5.2345","volume":"74","author":"JC Coleridge","year":"1993","unstructured":"Coleridge, J. C., Coleridge, H. M., Schelegle, E. S. & Green, J. F. Acute inhalation of ozone stimulates bronchial C-fibers and rapidly adapting receptors in dogs. J. Appl. Physiol. 74, 2345\u20132352 (1993).","journal-title":"J. Appl. Physiol."},{"key":"40343_CR41","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1089\/0894268041457147","volume":"17","author":"WG Kreyling","year":"2004","unstructured":"Kreyling, W. G., Semmler, M. & Moller, W. Dosimetry and toxicology of ultrafine particles. J. Aerosol. Med. 17, 140\u2013152 (2004).","journal-title":"J. Aerosol. Med."},{"key":"40343_CR42","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1080\/08958370490439650","volume":"16","author":"M Semmler","year":"2004","unstructured":"Semmler, M. et al. Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal. Toxicol. 16, 453\u2013459 (2004).","journal-title":"Inhal. Toxicol."},{"key":"40343_CR43","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.1161\/01.CIR.0000130847.18666.39","volume":"109","author":"S Vincent","year":"2004","unstructured":"Vincent, S. et al. Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation 109, 3202\u20133207 (2004).","journal-title":"Circulation"},{"key":"40343_CR44","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1056\/NEJM200002243420803","volume":"342","author":"JR Shannon","year":"2000","unstructured":"Shannon, J. R. et al. Orthostatic intolerance and tachycardia associated with norepinephrine transporter deficiency. N. Engl. J. Med. 342, 541\u2013549 (2000).","journal-title":"N. Engl. J. Med."},{"key":"40343_CR45","doi-asserted-by":"publisher","first-page":"5130","DOI":"10.1210\/jc.2002-020533","volume":"87","author":"M Boschmann","year":"2002","unstructured":"Boschmann, M. et al. Norepinephrine transporter function and autonomic control of metabolism. J. Clin. Endocrinol. Metab. 87, 5130\u20135137 (2002).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"40343_CR46","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.jacc.2006.04.073","volume":"48","author":"C Schroeder","year":"2006","unstructured":"Schroeder, C. et al. Norepinephrine transporter inhibition prevents tilt-induced pre-syncope. J. Am. Coll. Cardiol. 48, 516\u2013522 (2006).","journal-title":"J. Am. Coll. Cardiol."},{"key":"40343_CR47","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1097\/JCP.0000000000000611","volume":"36","author":"PR Bieck","year":"2016","unstructured":"Bieck, P. R. et al. Dihydroxyphenylglycol as a Biomarker of Norepinephrine Transporter Inhibition by Atomoxetine: Human Model to Assess Central and Peripheral Effects of Dosing. J. Clin. Psychopharmacol. 36, 675\u2013683 (2016).","journal-title":"J. Clin. Psychopharmacol."},{"key":"40343_CR48","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1007\/s007020050121","volume":"105","author":"YT Tseng","year":"1998","unstructured":"Tseng, Y. T. & Padbury, J. F. Expression of a pulmonary endothelial norepinephrine transporter. J. Neural Transm. (Vienna) 105, 1187\u20131191 (1998).","journal-title":"J. Neural Transm. (Vienna)"},{"key":"40343_CR49","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/BF00168693","volume":"345","author":"LJ Bryan-Lluka","year":"1992","unstructured":"Bryan-Lluka, L. J., Westwood, N. N. & O\u2019Donnell, S. R. Vascular uptake of catecholamines in perfused lungs of the rat occurs by the same process as Uptake1 in noradrenergic neurones. Naunyn Schmiedebergs Arch Pharmacol 345, 319\u2013326 (1992).","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"40343_CR50","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S0163-7258(01)00144-9","volume":"91","author":"G Eisenhofer","year":"2001","unstructured":"Eisenhofer, G. The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol. Ther. 91, 35\u201362 (2001).","journal-title":"Pharmacol. Ther."},{"key":"40343_CR51","first-page":"L360","volume":"262","author":"G Eisenhofer","year":"1992","unstructured":"Eisenhofer, G., Smolich, J. J. & Esler, M. D. Different desipramine-sensitive pulmonary removals of plasma epinephrine and norepinephrine in dogs. Am. J. Physiol. 262, L360\u2013365 (1992).","journal-title":"Am. J. Physiol."},{"key":"40343_CR52","first-page":"R243","volume":"276","author":"JJ Smolich","year":"1999","unstructured":"Smolich, J. J., Cox, H. S. & Esler, M. D. Contribution of lungs to desipramine-induced changes in whole body catecholamine kinetics in newborn lambs. Am. J. Physiol. 276, R243\u2013R250 (1999).","journal-title":"Am. J. Physiol."},{"key":"40343_CR53","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.116.309279","volume":"119","author":"CA Pope III","year":"2016","unstructured":"Pope, C. A. III et al. Exposure to fine particulate air pollution is associated with endothelial injury and systemic inflammation. Circ. Res. 119, 1204\u20131214 (2016).","journal-title":"Circ. Res."},{"key":"40343_CR54","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1124\/pr.108.000869","volume":"63","author":"AS Kristensen","year":"2011","unstructured":"Kristensen, A. S. et al. SLC6 neurotransmitter transporters: structure, function, and regulation. Pharmacol. Rev. 63, 585\u2013640 (2011).","journal-title":"Pharmacol. Rev."},{"key":"40343_CR55","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1080\/08958370500515913","volume":"18","author":"PA Steerenberg","year":"2006","unstructured":"Steerenberg, P. A. et al. Relation between sources of particulate air pollution and biological effect parameters in samples from four European cities: an exploratory study. Inhal. Toxicol. 18, 333\u2013346 (2006).","journal-title":"Inhal. Toxicol."},{"key":"40343_CR56","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1108\/eb006513","volume":"7","author":"P Appleby","year":"1989","unstructured":"Appleby, P. Fresh air and indoor air quality: Pieces in the sick building puzzle? Facilities 7, 7\u201311 (1989).","journal-title":"Facilities"},{"key":"40343_CR57","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1161\/HYPERTENSIONAHA.109.130237","volume":"54","author":"RD Brook","year":"2009","unstructured":"Brook, R. D. et al. Insights into the mechanisms and mediators of the effects of air pollution exposure on blood pressure and vascular function in healthy humans. Hypertension 54, 659\u2013667 (2009).","journal-title":"Hypertension"},{"key":"40343_CR58","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.envres.2016.06.014","volume":"150","author":"A Recio","year":"2016","unstructured":"Recio, A., Linares, C., Banegas, J. R. & Diaz, J. The short-term association of road traffic noise with cardiovascular, respiratory, and diabetes-related mortality. Environ. Res. 150, 383\u2013390 (2016).","journal-title":"Environ. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40343-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40343-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40343-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T07:03:10Z","timestamp":1671260590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40343-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,6]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["40343"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-40343-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,6]]},"assertion":[{"value":"19 June 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3641"}}