title: Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats.
abstract: Wistar rats were exposed for 4 hours by nose-only inhalation to clean air, resuspended Ottawa ambient particles (EHC-93*, 48 mg/m3), the water-leached particles (EHC-93L, 49 mg/m3), diesel soot (5 mg/m3), or carbon black (5 mg/m3). Continuous data for physiologic endpoints (heart rate, blood pressure, body temperature, animal's activity) were captured by telemetry before and after exposure. Blood was sampled from jugular cannulas 1 to 3 days before exposure and at 2 and 24 hours after exposure, and by heart puncture on termination at 32 hours (histology group) or 48 hours (telemetry group) after exposure. Lung injury was assessed by 3H-thymidine autoradiography after the rats were killed. We measured endothelins (plasma ET-1, big ET-1, ET-2, ET-3) to assess the vasopressor components; nitric oxide (NO)-related metabolites (blood nitrate, nitrite, nitrosyl compounds, and plasma 3-nitrotyrosine) to assess the vasodilator components; and catecholamines (epinephrine, norepinephrine, L-DOPA, dopamine) and oxidative stressors (m- and o-tyrosine) for additional insight into possible stress components. Lung cell labeling was uniformly low in all treatment groups, which indicates an absence of acute lung injury. Inhalation of EHC-93 caused statistically significant elevations (P < 0.05) of blood pressure on day 2 after exposure, plasma ET-1 at 32 hours after exposure, and ET-3 at 2, 32, and 48 hours after exposure. In contrast, the modified EHC-93L particles, from which soluble components had been extracted, did not affect blood pressure. The EHC-93L particles caused early elevation (P < 0.05) of the plasma levels of ET-1, ET-2, and ET-3 at 2 hours after exposure, but the endothelins returned to basal levels 32 hours after exposure. Exposure to diesel soot, but not carbon black, caused an elevation (P < 0.05) of plasma ET-3 at 36 hours after exposure; blood pressure was not affected by diesel soot. Our results indicate that inhalation of the urban particles EHC-93 can affect blood levels of ET-1 and ET-3 and cause a vasopressor response in Wistar rats without causing acute lung injury. Furthermore, the potency of the particles to influence hemodynamic changes appears to be modified by removing polar organic compounds and soluble elements. Because the pathophysiologic significance of elevated endothelins has been clinically established in humans, our observations suggest a novel mechanism by which inhaled particles may cause cardiovascular effects. These findings in rats contribute to the weight of evidence in favor of a biologically plausible epidemiologic association between ambient particulate matter and cardiovascular morbidity and mortality in human populations.
authors.affiliation: Safe Environments Programme, Health Canada, Ottawa, Ontario.
authors.forename: R
authors.initials: R
authors.lastname: Vincent
authors.forename: P
authors.initials: P
authors.lastname: Kumarathasan
authors.forename: P
authors.initials: P
authors.lastname: Goegan
authors.forename: S G
authors.initials: SG
authors.lastname: Bjarnason
authors.forename: J
authors.initials: J
authors.lastname: Guénette
authors.forename: D
authors.initials: D
authors.lastname: Bérubé
authors.forename: I Y
authors.initials: IY
authors.lastname: Adamson
authors.forename: S
authors.initials: S
authors.lastname: Desjardins
authors.forename: R T
authors.initials: RT
authors.lastname: Burnett
authors.forename: F J
authors.initials: FJ
authors.lastname: Miller
authors.forename: B
authors.initials: B
authors.lastname: Battistini
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D016232:Endothelins / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000033:anatomy & histology; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000097:blood; D014504:Urban Health
chemical_list: D000393:Air Pollutants; D002395:Catecholamines; D016232:Endothelins; D009569:Nitric Oxide; D014443:Tyrosine