You are here:
AIR PARTICULATE POLLUTION CARDIOVASCULAR TOXICITY: HAZARD IDENTIFICATION AND MECHANISMS OF ACTION
Citation:
Dreher, K L. AIR PARTICULATE POLLUTION CARDIOVASCULAR TOXICITY: HAZARD IDENTIFICATION AND MECHANISMS OF ACTION. Presented at British Association for Lung Research, Leicester, UK, Sept. 13-15, 2004.
Description:
The overall weight of evidence from epidemiological studies has shown statistical associations between air particulate pollution exposure and mortality\morbidity particularly within individuals with cardiovascular disease (1-4). Identification of causal particle properties and biological mechanisms responsible for these epidemiological associations remain a focus of intense research. Evidence from panel, clinical and toxicological studies has provided significant insight into the causal properties (5-10) and potential mechanisms of air particulate pollution cardiovascular toxicity (11-21). Particle size and composition, particularly bioavailable transition metal content, have been shown to represent physicochemical properties responsible for the cardiovascular toxicity of air pollution particles. Numerous hypotheses including systemic inflammation, altered autonomic cardiac control and vascular tone, as well as clotting factors have been proposed as mechanisms by which air particulate pollution affects the cardiovascular system. Research has employed organ perfusion methods in order to determine the ability of soluble constituents of air pollution particles to directly affect cardiovascular function ex vivo as well as identify effect modifiers. Langendorff perfused rat hearts exposed to a particle-free leachate (L) of residual oil fly ash (ROFA) produced a dose dependent decrease in flow rate and left ventricular developed pressure as well as an increase arrhythmia frequency. Alterations in ex vivo cardiac function were reproduced by a surrogate metal mixture and inhibited by antioxidant treatment. The ability of ROFA-L to alter vascular function in arteries taken from healthy and type 2 diabetic rats has been examined. Aortic ring contractile force was measured following exposure to various doses of a ROFA-L and phenylepherine (PE). ROFA-L produced a dose dependent increase in PE-mediated contractility in both healthy and diabetic aortas. At lower ROFA-L doses diabetic aortas displayed a greater PE-induced contractile response when compared to healthy aortas. A strong ROFA-L induced contractile response was observed only in diabetic aortas following the initial ROFA-L exposure with subsequent PE stimulation. Acetylcholine-mediated vascular relaxation was inhibited to a greater extent in diabetic aortas when compared to healthy aortas following ROFA-L exposure. These results provide additional mechanistic insight into alterations in cardiovascular function by air particulate pollution by demonstrating that: 1) bioavailable constituents can act directly to impair cardiovascular function; 2) exposure history and disease status maybe critical in modulating vascular functional responses; and 3) aortas from Type 2 diabetic rats were more sensitive to alterations in vascular function. (This abstract does not reflect EPA Policy)