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EFFECT OF OIL COMBUSTION PARTICLE BIOAVAILABLE CONSTITUENTS ON EX VIVO VASCULAR FUNCTION OF AORTAS RECOVERED FROM NORMAL AND TYPE 2 DIABETIC RATS
Citation:
Dreher, K L., S. E. Kelly, S. D. Proctor, AND J. C. Russell. EFFECT OF OIL COMBUSTION PARTICLE BIOAVAILABLE CONSTITUENTS ON EX VIVO VASCULAR FUNCTION OF AORTAS RECOVERED FROM NORMAL AND TYPE 2 DIABETIC RATS. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Effect of Oil Combustion Particle Bioavailable Constituents on Ex Vivo Vascular Function of Aortae Recovered from Healthy and Early Type 2 Diabetic Rats
KL Dreher1, SE Kelly2, SD Proctor2, and JC Russell2. 1National Health and Environmental Effects Laboratory, US EPA, RTP, NC; 2University of Alberta, Edmonton, Canada
Epidemiological studies have reported statistical associations between air particulate pollution exposure and alterations in cardiovascular function particularly in individuals with recent myocardial infarctions or Type 2 diabetes. However, the physicochemical properties of particles and biological mechanisms responsible for these observations are not known. This study examines the ability of soluble constituents of air pollution particles to alter vascular function in arteries from healthy and Type 2 diabetic JCR:LA-cp rats. Aortic rings recovered from normal and diabetic rats were maintained in oxygenated Krebs Henseleit buffer at 37oC. Contractile force was measured for each aortic ring following exposure to various doses of a particle-free leachate of residual oil fly ash (ROFA-L) (1.5 ? 12.5 mg/ml) and phenylepherine (PE) (10-9 - 10-3 M). ROFA-L exposure produced a dose dependent increase in PE-mediated vascular contractility in the aortae from both healthy and diabetic rats. However, at the lowest concentration of ROFA- L (1.5 mg/ml) diabetic aortae displayed a greater PE-induced contractile response when compared to aortae recovered from normal rats. Interestingly, a very strong ROFA-L induced vascular contractile response was observed only in diabetic aortae following the initial ROFA-L exposure with subsequent PE stimulation. Finally, acetylcholine-mediated vascular relaxation was inhibited to a greater extent in diabetic aortae when compared to healthy aortae following exposure to higher ROFA-L doses (6.25 and 12.5 mg/ml). Our results demonstrate that: 1) bioavailable constituents of oil combustion particles can impair vascular function; 2) exposure history and disease status maybe critical to this response; and 3) aortae from Type 2 diabetic rats were found to be more sensitive to alterations in vascular responsivenessfollowing exposure to bioavailable constituents associated with oil combustion particles. (This abstract does not reflect EPA Poli