title: Morning NO2 exposure sensitizes hypertensive rats to the cardiovascular effects of same day O3 exposure in the afternoon.
abstract: BACKGROUND
  Within urban air sheds, specific ambient air pollutants typically peak at predictable times throughout the day. For example, in environments dominated by mobile sources, peak nitrogen dioxide (NO2) levels coincide with morning and afternoon rush hours, while peak levels of ozone (O3), occur in the afternoon.
  
  
  OBJECTIVE
  Given that exposure to a single pollutant might sensitize the cardiopulmonary system to the effects of a subsequent exposure to a second pollutant, we hypothesized that a morning exposure to NO2 will exaggerate the cardiovascular effects of an afternoon O3 exposure in rats.
  
  
  METHODS
  Rats were divided into four groups that were each exposed for 3 h in the morning (m) and 3 h in the afternoon (a) on the same day: (1) m-Air/a-Air, (2) m-Air/a-O3 (0.3 ppm), (3) m-NO2 (0.5 ppm)/a-Air and (4) m-NO2/a-O3. Implanted telemetry devices recorded blood pressure and electrocardiographic data. Sensitivity to the arrhythmogenic agent aconitine was measured in a separate cohort.
  
  
  RESULTS
  Only m-NO2/a-O3-exposed rats had significant changes in electrophysiological, mechanical and autonomic parameters. These included decreased heart rate and increased PR and QTc intervals and increased heart rate variability, suggesting increased parasympathetic tone. In addition, only m-NO2/a-O3 exposure decreased systolic and diastolic blood pressures and increased pulse pressure and QA interval, suggesting decreased cardiac contractility.
  
  
  CONCLUSIONS
  The findings indicate that initial exposure to NO2 sensitized rats to the cardiovascular effects of O3 and may provide insight into the epidemiological data linking adverse cardiovascular outcomes with exposures to low concentrations of O3.
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Aimen K
authors.initials: AK
authors.lastname: Farraj
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Malik
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Najwa
authors.initials: N
authors.lastname: Haykal-Coates
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Walsh
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Darrell
authors.initials: D
authors.lastname: Winsett
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Dock
authors.initials: D
authors.lastname: Terrell
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Thompson
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Cascio
authors.affiliation: a Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park , NC , USA.
authors.forename: Mehdi S
authors.initials: MS
authors.lastname: Hazari
mesh_terms: D000157:Aconitine; D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000393:Air Pollutants; D010126:Ozone; D009585:Nitrogen Dioxide; D000157:Aconitine
keywords: Air pollution, blood pressure; cardiovascular; electrocardiogram; nitrogen dioxide; ozone; sequential exposure