The spontaneously hypertensive rat: an experimental model of sulfur dioxide-induced airways disease.

Published

Journal Article

Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation, and mucus hypersecretion, features that are common in 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, hypercoagulation, 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- to 15-weeks old) to 0, 250, or 350 ppm sulfur dioxide (SO(2)), 5 h/day for 4 consecutive days to induce airway injury. SO(2) caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD rats. Increases in 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 at 4 days following SO(2) 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 SO(2) 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. SO(2) effects on these genes were more pronounced in SH than in SD rats. Thus, SO(2) exposure in SH rats may yield a relevant experimental model of bronchitis.

Full Text

Duke Authors

Cited Authors

  • Kodavanti, UP; Schladweiler, MC; Ledbetter, AD; Ortuno, RV; Suffia, M; Evansky, P; Richards, JH; Jaskot, RH; Thomas, R; Karoly, E; Huang, Y-CT; Costa, DL; Gilmour, PS; Pinkerton, KE

Published Date

  • November 2006

Published In

Volume / Issue

  • 94 / 1

Start / End Page

  • 193 - 205

PubMed ID

  • 16929007

Pubmed Central ID

  • 16929007

Electronic International Standard Serial Number (EISSN)

  • 1096-0929

International Standard Serial Number (ISSN)

  • 1096-6080

Digital Object Identifier (DOI)

  • 10.1093/toxsci/kfl087

Language

  • eng