title: Nonparticulate components of diesel exhaust promote constriction in coronary arteries from ApoE-/- mice.
abstract: Air pollution is positively associated with increased daily incidence of myocardial infarction and cardiovascular mortality. We hypothesize that air pollutants, primarily vapor phase organic compounds, cause an enhancement of coronary vascular constriction. Such events may predispose susceptible individuals to anginal symptoms and/or exacerbation of infarction. To develop this hypothesis, we studied the effects of nonparticulate diesel exhaust constituents on (1) electrocardiographic traces from ApoE-/- mice exposed whole-body and (2) isolated, pressurized septal coronary arteries from ApoE-/- mice. ApoE-/- mice were implanted with radiotelemetry devices to assess electrocardiogram (ECG) waveforms continuously throughout exposures (6 h/day x 3 days) to diesel exhaust (0.5 and 3.6 mg/m3) in whole-body inhalation chambers with or without particulates filtered. Significant bradycardia and T-wave depression were observed, regardless of the presence of particulates. Pulmonary inflammation was present only in the whole exhaust-exposed animals at the highest concentration. Fresh diesel exhaust or air was bubbled through the physiologic saline tissue bath prior to experiments to enable the isolated tissue exposure; exposed saline contained elevated levels of several volatile carbonyls and alkanes, but low to absent levels of polycyclic aromatic hydrocarbons. Vessels were then assayed for constrictive and dilatory function. Diesel components enhanced the vasoconstrictive effects of endothelin-1 and reduced the dilatory response to sodium nitroprusside. These data demonstrate that nonparticulate compounds in whole diesel exhaust elicit ECG changes consistent with myocardial ischemia. Furthermore, the volatile organic compounds in the vapor phase caused enhanced constriction and reduced dilatation in isolated coronary arteries caused by nonparticulate components of diesel exhaust.
authors.affiliation: Department of Toxicology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. mcampen@LRRI.org
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
authors.forename: N Sathish
authors.initials: NS
authors.lastname: Babu
authors.forename: G Andrew
authors.initials: GA
authors.lastname: Helms
authors.forename: Stuart
authors.initials: S
authors.lastname: Pett
authors.forename: Jorge
authors.initials: J
authors.lastname: Wernly
authors.forename: Reza
authors.initials: R
authors.lastname: Mehran
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019570:Inhalation Exposure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009930:Organic Chemicals / Q000737:chemistry / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D013686:Telemetry; D014661:Vasoconstriction / Q000187:drug effects*; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*; D014835:Volatilization
chemical_list: D000393:Air Pollutants; D009930:Organic Chemicals; D001335:Vehicle Emissions