Hypersensitivity of Prediabetic JCR:LA-cp Rats to Fine Airborne Combustion Particle-Induced Direct and Noradrenergic-Mediated Vascular Contraction
Particulate matter with mean aerodynamic diameter ≤2.5 μm (PM2.5), from diesel exhaust, coal or residual oil burning, and from industrial plants, is a significant component of airborne pollution. Type 2 diabetes is associated with enhanced risk of adverse cardiovascular events following exposure to...
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Published in | Toxicological sciences Vol. 90; no. 2; pp. 385 - 391 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Oxford University Press
01.04.2006
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Subjects | |
Online Access | Get full text |
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Summary: | Particulate matter with mean aerodynamic diameter ≤2.5 μm (PM2.5), from diesel exhaust, coal or residual oil burning, and from industrial plants, is a significant component of airborne pollution. Type 2 diabetes is associated with enhanced risk of adverse cardiovascular events following exposure to PM2.5. Particle properties, sources, and pathophysiological mechanisms responsible are unknown. We studied effects of residual oil fly ash (ROFA) from a large U.S. powerplant on vascular function in a prediabetic, hyperinsulinemic model, the JCR:LA-cp rat. Residual oil fly ash leachate (ROFA-L) was studied using aortic rings from young-adult, obese, insulin-resistant rats and lean normal rats in vitro. Contractile response to phenylephrine and relaxant response to acetylcholine were determined in the presence and absence of L-NAME (NG-nitro-L-arginine methyl ester). In a separate series of studies, the direct contractile effects of ROFA-L on repeated exposure were determined. ROFA-L (12.5 μg ml−1) increased phenylephrine-mediated contraction in obese (p < 0.05), but not in lean rat aortae, with the effect being exacerbated by L-NAME, and it reduced acetylcholine-mediated relaxation of both obese and lean aortae (p < 0.0001). Initial exposure of aortae to ROFA-L caused a small contractile response (<0.05 g), which was markedly greater on second exposure in the obese (∼0.6 g, p < 0.0001) aortae but marginal in lean (∼0.1 g) aortae. Our data demonstrate that bioavailable constituents of oil combustion particles enhance noradrenergic-mediated vascular contraction, impair endothelium-mediated relaxation, and induce direct vasocontraction in prediabetic rats. These observations provide the first direct evidence of the causal properties of PM2.5 and identify the pathophysiological role of the early prediabetic state in susceptibility to environmentally induced cardiovascular disease. These are important implications for public health and public policy. |
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Bibliography: | ark:/67375/HXZ-28QCSP6R-6 istex:C162797FB4553EEB6FF6241A9BD0D3FAC18F727F local:kfj100 1To whom correspondence should be addressed at Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, 4–10 Agriculture Forestry Centre, University of Alberta, Edmonton, AB, T6G 2P5, Canada. E-mail: Jim.Russell@ualberta.ca. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1096-6080 1096-0929 |
DOI: | 10.1093/toxsci/kfj100 |