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SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO AIRWAY DISEASE INDUCED BY SULFUR DIOXIDE
Citation:
Schladweiler, M., A. D. Ledbetter, D L. Costa, K. E. Pinkerton, J H. Richards, P. E. Evansky, AND U P. Kodavanti. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO AIRWAY DISEASE INDUCED BY SULFUR DIOXIDE. Presented at Society of Toxicology Annual Meeting, New Orleans, LA, March 06 - 10, 2005.
Description:
Rodent models of chronic pulmonary diseases induced by sulfur dioxide (SO2), elastase or tobacco smoke have limited utility because of their lack of chronicity of inflammation, and they demonstrate limited sensitivity to a given experimental manipulation. We hypothesized that disease susceptibility from experimental exposures require unique genetic predisposition. Spontaneously hypertensive (SH) rats, with genetic susceptibility to cardiovascular disease, and healthy Sprague Dawely (SD) rats were exposed: 1) nose-only to SO2 at 0, 250 or 350 ppmx5h/dx4d; 2) to porcine pancreatic elastase (PPE), intratracheal (IT) at 0, 400, 800 or 1200 U/kg; or 3) to SO2 (only SH rats pre-exposed to PPE at 0 or 800 U/Kg, IT, 1 week prior) at 0 or 350 ppm, 5h/dx4d. Pulmonary functional and biological impairments were evaluated. PPE caused severe pulmonary injury and inflammation in SD rats. The severity of acute injury was less in SH rats but inflammation persisted for a longer time following exposure. In contrast to PPE, SO2-induced neutrophilic inflammation was 30-40 fold higher in SH than in SD rats, and was associated with an increase in alveolar macrophages. These changes in SH rats persisted for up to 7 days. Although the inflammatory response was higher in SH rats, SO2-induced changes in breathing parameters were not significantly different between SH and SD rats. We then hypothesized that SO2-induced inflammation would be more severe in PPE-pretreated SH rats. Neither pulmonary injury nor inflammation was greater in PPE-pretreated SH rats, except for a slightly greater increase in alveolar macrophages. Similarly, the plethysmographic measurement of breathing parameters indicated marginally greater PenH values following the PPE+SO2 exposure. In conclusion, SH rats demonstrated several fold greater inflammatory response to SO2 than SD rats, but the strain differences were not marked in regards to effects on breathing parameters. Also, PPE-induced injury is not exacerbated by subsequent SO2 exposure. (Does not reflect US EPA policy).