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COMPARATIVE EVALUATION OF RISK FACTORS FOR CARDIOVASCULAR DISEASE (CVD) IN GENETICALLY PREDISPOSED RATS
Citation:
SCHLADWEILER, M., A. NYSKA, A. D. LEDBETTER, G. WALLENBORN, R. R. GOTTIPOLU, J. E. RICHARDS, R. THOMAS, R. H. JASKOT, J. SHANNAHAN, K. M. CRISSMAN, G. E. HATCH, AND U. P. KODAVANTI. COMPARATIVE EVALUATION OF RISK FACTORS FOR CARDIOVASCULAR DISEASE (CVD) IN GENETICALLY PREDISPOSED RATS. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Rodent CVD models are increasingly used for understanding individual differences in susceptibility to environmental stressors such as air pollution. We characterized pathologies and a number of known human risk factors of CVD in genetically predisposed, male young adult Spontaneously Hypertensive (SH), Stroke-Prone SH (SHSP), Heart Failure SH (SHHF) and Diabetic (JCR) rats. These were compared to healthy Sprague Dawley (SD) and parental Wistar Kyoto (WKY) rats. Baseline differences in pathology of the heart, lung and kidney, antioxidants and gene expression, along with levels of systemic inflammation and coagulation markers were analyzed to understand distinct disease-related phenotypes. There were various degrees of myopathy in all strains; JCR appeared to be affected the most. No major pathological lesions were apparent in the lungs of any strain. However, lavage fluid neutrophils, marker for lung inflammation, were increased in SH and SHSP relative to others. This was associated with higher baseline levels of lung glutathione but lower ascorbate. Lung ascorbate levels were highest in SD and JCR. Although having high hematocrit values, coagulation parameters in JCR were comparable to WKY. These were most affected in SHSP relative to WKY. JCR and SD rats had the highest number of circulating white blood cells and lymphocytes relative to all other strains. Further, JCR and SHHF, both with obese phenotype, demonstrated remarkable kidney lesions. Thus, each model demonstrates distinct disease- and tissue-dependent anomalies that are likely to be associated with the degree of compensatory response. Understanding the pathobiologic manifestations of the disease in the chosen animal model is essential for accurate interpretation of susceptibility data. (This abstract does not reflect US EPA policy. Supported in part by UNC/EPA CT829471 and NRC Research Associateship Award at NHEERL, EPA).