Ozone inhalation impairs coronary artery dilation via intracellular oxidative stress: evidence for serum-borne factors as drivers of systemic toxicity
Open accessAbstract
Ambient ozone (O3) levels are associated with cardiovascular morbidity and mortality, but the underlying pathophysiological mechanisms driving extrapulmonary toxicity remain unclear. This study examined the coronary vascular bed of rats in terms of constrictive and dilatory responses to known agonists following a single O3 inhalation exposure. In addition, serum from exposed rats was used in ex vivo preparations to examine whether bioactivity and toxic effects of inhaled O3 could be conveyed to extrapulmonary systems via the circulation. We found that 24 h following inhalation of 1 ppm O3, isolated coronary vessels exhibited greater basal tone and constricted to a greater degree to serotonin stimulation. Vasodilation to acetylcholine (ACh) was markedly diminished in coronary arteries from O3-exposed rats, compared with filtered air-exposed controls. Dilation to ACh was restored by combined superoxide dismutase and catalase treatment, and also by NADPH oxidase inhibition. When dilute (10%) serum from exposed rats was perfused into the lumen of coronary arteries from unexposed, naïve rats, the O3-induced reduction in vasodilatory response to ACh was partially recapitulated. Furthermore, following O3 inhalation, serum exhibited a nitric oxide scavenging capacity, which may partially explain blunted ACh-mediated vasodilatory responses. Thus, bioactivity from inhalation exposures may be due to compositional changes of the circulation. These studies shed light on possible mechanisms of action that may explain O3-associated cardiac morbidity and mortality in humans.
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Animal studies with high ozone exposures have generated more consistent findings on cardiovascular effects of ozone through altering vascular tone, mRNA for genes encoding thrombogenic factors, and atherogenesis.
“In contrast, animal studies with high ozone exposures have generated more consistent findings on cardiovascular effects of ozone through altering vascular tone (60–62), mRNA for genes encoding thrombogenic factors (63), and atherogenesis (60).”
From Ozone pollution: A Major health hazard worldwide (2019) · cites this paper as [61]
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Cites
Global association of air pollution and heart failure: a systematic review and meta-analysis
Shah, A. S. V., Langrish, J. P., Nair, H., McAllister, D., Hunter, A. L., Donaldson, K., Newby, D. E., & Mills, N. L. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60898-3 · Cited by 1,231 · see citing works
Ozone and short-term mortality in 95 US urban communities, 1987–2000
Bell, M. L. (2004) · JAMA · doi:10.1001/jama.292.19.2372 · Cited by 1,202 · see citing works
Sun, Q. (2005) · JAMA · doi:10.1001/jama.294.23.3003 · Cited by 850 · see citing works
Brook, R. D., Brook, J. R., Urch, B., Vincent, R., Rajagopalan, S., & Silverman, F. (2002) · Circulation · doi:10.1161/01.cir.0000013838.94747.64 · Cited by 845 · see citing works
Main Air Pollutants and Myocardial Infarction
Mustafić, H., Jabre, P., Caussin, C., Murad, M. H., Escolano, S., Tafflet, M., Perier, M., Marijon, É., Vernerey, D., Empana, J. P., et al. (2012) · JAMA · doi:10.1001/jama.2012.126 · Cited by 816 · see citing works
The Biotin Switch Method for the Detection of S -Nitrosylated Proteins
Jaffrey, S. R., & Snyder, S. H. (2001) · Science s STKE · doi:10.1126/stke.2001.86.pl1 · Cited by 805 · see citing works
How far does ozone penetrate into the pulmonary air/tissue boundary before it reacts?
Pryor, W. A. (1992) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(92)90060-t · Cited by 270 · see citing works
Systemic Microvascular Dysfunction and Inflammation after Pulmonary Particulate Matter Exposure
Nurkiewicz, T. R., Porter, D. W., Barger, M. W., Millecchia, L., Rao, K. M. K., Marvar, P. J., Hubbs, A. F., Castranova, V., & Boegehold, M. A. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.8413 · Cited by 267 · see citing works
Hatch, G. E., Slade, R., Harris, L. P., McDonnell, W. F., Devlin, R. B., Koren, H. S., Costa, D. L., & McKee, J. M. T. (1994) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.150.3.8087337 · Cited by 239 · see citing works
Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation
Mills, N. L., Miller, M. R., Lucking, A. J., Beveridge, J., Flint, L., Boere, A. J. F., Fokkens, P. H. B., Boon, N. A., Sandström, T., Blomberg, A., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr195 · Cited by 221 · see citing works
Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects
Devlin, R. B., Duncan, K., Jardim, M. J., Schmitt, M. T., Rappold, A. G., & Díaz-Sánchez, D. (2012) · Circulation · doi:10.1161/circulationaha.112.094359 · Cited by 220 · see citing works
Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling
Nurkiewicz, T. R., Porter, D. W., Hubbs, A. F., Stone, S., Chen, B. T., Frazer, D. G., Boegehold, M. A., & Castranova, V. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp051 · Cited by 147 · see citing works
Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis
Chuang, G. C., Yang, Z., Westbrook, D. G., Pompilius, M., Ballinger, C. A., White, C. R., Krzywanski, D. M., Postlethwait, E. M., & Ballinger, S. W. (2009) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00102.2009 · Cited by 145 · see citing works
Wood, K. C., Cortese-Krott, M. M., Kovacic, J. C., Noguchi, A. C., Liu, V. B., Wang, X., Raghavachari, N., Boehm, M., Kato, G. J., Kelm, M., et al. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.301068 · Cited by 123 · see citing works
Watkinson, W. P., Campen, M. J., Nolan, J. P., & Costa, D. L. (2001) · Environmental Health Perspectives · doi:10.1289/ehp.01109s4539 · Cited by 118 · see citing works
Self-citationThe Oxidized Low-Density Lipoprotein Receptor Mediates Vascular Effects of Inhaled Vehicle Emissions
Lund, A. K., Lucero, J., Harman, M., Madden, M. C., McDonald, J. D., Seagrave, J., & Campen, M. J. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201012-1967oc · Cited by 116 · see citing works
Self-citationShort-term effects of air pollution on out-of-hospital cardiac arrest in Stockholm
Raza, A., Bellander, T., Bedada, G. B., Dahlquist, M., Hollenberg, J., Jonsson, M. N., Lind, T., Rosenqvist, M., Svensson, L. A., & Ljungman, P. L. S. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht489 · Cited by 111 · see citing works
Conklin, D. J., Haberzettl, P., Prough, R. A., & Bhatnagar, A. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00867.2008 · Cited by 110 · see citing works
Campen, M. J., Babu, N. S., Helms, G. A., Pett, S. B., Wernly, J. A., Mehran, R. J., & McDonald, J. D. (2005) · Toxicological Sciences · doi:10.1093/toxsci/kfi283 · Cited by 99 · see citing works
Self-citationMechanisms of Diesel-Induced Endothelial Nitric Oxide Synthase Dysfunction in Coronary Arterioles
Cherng, T. W., Paffett, M. L., Jackson‐Weaver, O., Campen, M. J., Walker, B. R., & Kanagy, N. L. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.1002286 · Cited by 97 · see citing works
Self-citationDiesel exhaust particles induce endothelial dysfunction in apoE−/− mice
Hansen, C. S., Sheykhzade, M., Möller, P., Folkmann, J. K., Amtorp, O., Jonassen, T. E. N., & Loft, S. H. (2006) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2006.10.032 · Cited by 96 · see citing works
Channell, M. M., Paffett, M. L., Devlin, R. B., Madden, M. C., & Campen, M. J. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs084 · Cited by 93 · see citing works
Self-citationWagner, J. G., Allen, K. M., Yang, H.-Y., Nan, B., Morishita, M., Mukherjee, B., Dvonch, J. T., Spino, C., Fink, G. D., Rajagopalan, S., et al. (2013) · Environmental Health Perspectives · doi:10.1289/ehp.1307085 · Cited by 88 · see citing works
Sun, L., Liu, C., Xu, X., Ying, Z., Maiseyeu, A., Wang, A., Allen, K. M., Lewandowski, R. P., Bramble, L. A., Morishita, M., et al. (2013) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-10-43 · Cited by 84 · see citing works
Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS
Knuckles, T. L., Lund, A. K., Lucas, S., & Campen, M. J. (2008) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2008.03.010 · Cited by 83 · see citing works
Self-citationCD36 mediates endothelial dysfunction downstream of circulating factors induced by O3 exposure
Robertson, S., Colombo, E. S., Lucas, S. N., Hall, P. R., Febbraio, M., Paffett, M. L., & Campen, M. J. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft107 · Cited by 82 · see citing works
Self-citationTracing the Origins of Autism: A Spectrum of New Studies
Szpir, M. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.114-a412 · Cited by 76 · see citing works
Cherng, T. W., Campen, M. J., Knuckles, T. L., Bosc, L. V. G., & Kanagy, N. L. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90899.2008 · Cited by 72 · see citing works
Self-citationMeta-analysis of the Chinese studies of the association between ambient ozone and mortality
Yan, M., Zhaorong, L., Liu, X., Duan, H., & Li, T. (2013) · Chemosphere · doi:10.1016/j.chemosphere.2013.05.040 · Cited by 62 · see citing works
Cooking Up Indoor Air Pollution: Emissions from Natural Gas Stoves
Nicole, W. (2013) · Environmental Health Perspectives · doi:10.1289/ehp.122-a27 · Cited by 60 · see citing works
Kadiiska, M. B., Basu, S., Brot, N., Cooper, C. E., Csallany, A. S., Davies, M. J., George, M. M., Murray, D. M., Roberts, L. J., Shigenaga, M. K., et al. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.04.023 · Cited by 59 · see citing works
Determinants of Inhaled Ozone Absorption in Isolated Rat Lungs
Postlethwait, E. M., Langford, S. D., & Bidani, A. (1994) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1994.1051 · Cited by 55 · see citing works
Barath, S., Langrish, J. P., Lundbäck, M., Bosson, J. A., Goudie, C. R., Newby, D. E., Sandström, T., Mills, N. L., & Blomberg, A. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft157 · Cited by 54 · see citing works
Merx, M. W., Gorressen, S., Sandt, A. M., Cortese-Krott, M. M., Ohlig, J., Stern, M., Rassaf, T., Gödecke, A., Gladwin, M. T., & Kelm, M. (2014) · Basic Research in Cardiology · doi:10.1007/s00395-013-0398-1 · Cited by 53 · see citing works
Farraj, A. K., Hazari, M. S., Winsett, D. W., Kulukulualani, A., Carll, A. P., Haykal-Coates, N., Lamb, C. M., Lappi, E., Terrell, D., Cascio, W. E., et al. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1104244 · Cited by 43 · see citing works
Ozone short-term exposure and acute coronary events: A multicities study in Tuscany (Italy)
Nuvolone, D., Balzi, D., Pepe, P., Chini, M., Scala, D., Giovannini, F., Cipriani, F., & Barchielli, A. (2013) · Environmental Research · doi:10.1016/j.envres.2013.08.002 · Cited by 41 · see citing works
Nurkiewicz, T. R., Wu, G., Li, P., & Boegehold, M. A. (2010) · Microcirculation · doi:10.1111/j.1549-8719.2009.00014.x · Cited by 36 · see citing works
Endothelium-dependent blunting of myogenic responsiveness after chronic hypoxia
Earley, S., & Walker, B. R. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00125.2002 · Cited by 32 · see citing works
Comparative Simulation of Gas Transport in Airway Models of Rat, Dog, and Human
Tsujino, I., Kawakami, Y., & Kaneko, A. (2005) · Inhalation Toxicology · doi:10.1080/08958370590964476 · Cited by 30 · see citing works
Gordon, C. J., Johnstone, A. F. M., Aydın, C., et al. (2014) · Inhalation Toxicology · doi:10.3109/08958378.2014.905659 · Cited by 29 · see citing works
Adaptation to Ozone in Rats and Its Association with Ascorbic Acid in the Lung
Wiester, M. J. (1996) · Fundamental and Applied Toxicology · doi:10.1006/faat.1996.0075 · Cited by 25 · see citing works
Rees, M. D., Maiocchi, S. L., Kettle, A. J., & Thomas, S. R. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.037 · Cited by 19 · see citing works
Acute Exposure to Ozone Exacerbates Acetaminophen-Induced Liver Injury in Mice
Aibo, D. I., Birmingham, N., Lewandowski, R. P., Maddox, J. F., Roth, R. A., Ganey, P. E., Wagner, J. G., & Harkema, J. R. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq034 · Cited by 18 · see citing works
Ozone Uptake in Healthy Adult Males during Quiet Breathing
Wiester, M. J., STEVENS, M. A., Ménache, M. G., McKee, J. L., & Gerrity, T. R. (1996) · Fundamental and Applied Toxicology · doi:10.1093/toxsci/29.1.102 · Cited by 17 · see citing works
Tankersley, C. G., Georgakopoulos, D., Tang, W., Abston, E. D., Bierman, A. M., & Sborz, N. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs273 · Cited by 17 · see citing works
Effects of Exercise on Oxidative Stress in Rats Induced by Ozone
Martínez-Campos, C., Lara‐Padilla, E., Bobadilla-Lugo, R. A., Kross, R. D., & Villanueva, C. (2012) · The Scientific World JOURNAL · doi:10.1100/2012/135921 · Cited by 13 · see citing works
Nitric Oxide Synthase: “Enzyme Zero” in Air Pollution–Induced Vascular Toxicity
Campen, M. J. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp078 · Cited by 12 · see citing works
Self-citationFate of Pathologically Bound Oxygen Resulting from Inhalation of Labeled Ozone in Rats
Hatch, G. E., Slade, R., & McKee, J. M. T. (2013) · Environmental Health Insights · doi:10.4137/ehi.s12673 · Cited by 8 · see citing works
Robinson, C. (2009) · Cited by 3 · see citing works
Short-term Effects of Air Pollution on Out-of-Hospital Cardiac Arrest
Raza, A., Bellander, T., Bedada, G. B., et al. (2013) · ISEE Conference Abstracts · doi:10.1289/isee.2013.p-3-05-34 · Cited by 3 · see citing works
Campen, M. J. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft169 · Cited by 1 · see citing works
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Day, D. B., Xiang, J., Mo, J., Li, F., Chung, M., Gong, J., Weschler, C. J., Ohman-Strickland, P. A., Sundell, J., Weng, W., et al. (2017) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2017.2842 · Cited by 264 · see citing works
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- Authors
- Paffett, M. L., Zychowski, K. E., Sheppard, L., Robertson, S., Weaver, J. M., Lucas, S. N., & Campen, M. J.
- Affiliations
- University of New Mexico (US)
- University of Washington (US)
- Public Health England (GB)
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05-11
- Volume
- 146
- Issue
- 2
- Pages
- 244-253
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- PMC
- PMC4607748
- OpenAlex
- W2103398685
- Cited by
- 67
- References
- 51
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 9 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 9 · 2016: 8 · 2015: 2
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (P30GM103400, K12GM088021)
- National Institute of Environmental Health Sciences (R01ES014639)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant responses to elevated CO2
- Keywords
- ozone inhalation, coronary artery dilation, oxidative stress, acetylcholine-induced vasodilation, serotonin-induced vasoconstriction, systemic toxicity, nitric oxide scavenging, superoxide dismutase, catalase, NADPH oxidase, cardiovascular effects of air pollution, coronary vasomotor tone
- MeSH terms
- Acetylcholine, Animals, Blood, Coronary Vessels, Male, Ozone, Serotonin, Vasodilation, Rats, Sprague-Dawley, Oxidative Stress, Inhalation Exposure, Mice, Rats
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