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THE SPONTANEOUSLY HYPERTENSIVE RAT: AN EXPERIMENTAL MODEL OF SULFUR DIOXIDE-INDUCED AIRWAYS DISEASE
Citation:
KODAVANTI, U. P., M. SCHLADWEILER, A. D. LEDBETTER, R. V. ORTUNO, M. SUFFIA, P. A. EVANSKY, J. E. RICHARDS, R. H. JASKOT, R. THOMAS, E. KAROLY, Y. T. HUANG, D. L. COSTA, P. GILMOUR, AND K. E. PINKERTON. THE SPONTANEOUSLY HYPERTENSIVE RAT: AN EXPERIMENTAL MODEL OF SULFUR DIOXIDE-INDUCED AIRWAYS DISEASE. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 94(1):193-205, (2006).
Impact/Purpose:
To determine whether spontaneously hypertensive (SH) rats offer a better model of experimental bronchitis
Description:
Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation and mucus hypersecretion; features that capture bronchitis, emphysema and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisposed spontaneously hypertensive (SH) rats display phenotypes such as systemic inflammation, thrombosis, oxidative stress, and suppressed immune function that are also apparent in COPD patients, we hypothesized that SH rat may offer a better model of experimental bronchitis. We therefore, exposed SH and commonly used Sprague Dawley (SD) rats (male, 13-15 wk old) to 0, 250, or 350 ppm sulfur dioxide (SO2), 5h/d for 4 consecutive days to induce airway injury. SO2 caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD. Bronchoalveolar lavage fluid (BALF) total cells and neutrophilic inflammation were dose-dependent and significantly greater in SH than in SD rats. The recovery was incomplete 4 days following SO2 exposure in SH rats. Pulmonary protein leakage was modest in either strain, but lactate dehydrogenase and n-acetyl glucosaminidase activity were increased in BALF of SH rats. Airway pathology and morphometric evaluation of mucin demonstrated significantly greater impact of SO2 in SH than in SD rats. Baseline differences in lung gene expression pattern suggested marked immune dysregulation, oxidative stress, impairment of cell signaling and fatty acid metabolism in SH rats. SO2 effects on these genes were more pronounced in SH than in SD rats. Thus, SO2 exposure in SH rats may yield a relevant experimental model of bronchitis.