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

Urmila P. Kodavanti, Mette C. Schladweiler, Allen D. Ledbetter, Roselia Villalobos Ortuno, Marie Suffia, Paul Evansky, Judy H. Richards, Richard H. Jaskot, Ronald Thomas, Edward Karoly, Yuh Chin T Huang, Daniel L. Costa, Peter S. Gilmour, Kent E Pinkerton

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 (SO2), 5 h/day 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 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 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.

Original languageEnglish (US)
Pages (from-to)193-205
Number of pages13
JournalToxicological Sciences
Volume94
Issue number1
DOIs
StatePublished - Nov 2006

Fingerprint

Sulfur Dioxide
Inbred SHR Rats
Rats
Theoretical Models
Sprague Dawley Rats
Bronchitis
Bronchoalveolar Lavage Fluid
Inflammation
Chronic Obstructive Pulmonary Disease
Oxidative Stress
Pulmonary diseases
Oxidative stress
Hexosaminidases
Lung
Emphysema
Mucins
Airway Obstruction
Mucus
L-Lactate Dehydrogenase
Rodentia

Keywords

  • Bronchitis
  • Chronic obstructive pulmonary disease
  • Inflammation
  • Mucus hypersecretion
  • Spontaneously hypertensive rats
  • Sulfur dioxide exposure

ASJC Scopus subject areas

  • Toxicology

Cite this

Kodavanti, U. P., Schladweiler, M. C., Ledbetter, A. D., Ortuno, R. V., Suffia, M., Evansky, P., ... Pinkerton, K. E. (2006). The spontaneously hypertensive rat: An experimental model of sulfur dioxide-induced airways disease. Toxicological Sciences, 94(1), 193-205. https://doi.org/10.1093/toxsci/kfl087

The spontaneously hypertensive rat : An experimental model of sulfur dioxide-induced airways disease. / Kodavanti, Urmila P.; Schladweiler, Mette C.; Ledbetter, Allen D.; Ortuno, Roselia Villalobos; Suffia, Marie; Evansky, Paul; Richards, Judy H.; Jaskot, Richard H.; Thomas, Ronald; Karoly, Edward; Huang, Yuh Chin T; Costa, Daniel L.; Gilmour, Peter S.; Pinkerton, Kent E.

In: Toxicological Sciences, Vol. 94, No. 1, 11.2006, p. 193-205.

Research output: Contribution to journalArticle

Kodavanti, UP, Schladweiler, MC, Ledbetter, AD, Ortuno, RV, Suffia, M, Evansky, P, Richards, JH, Jaskot, RH, Thomas, R, Karoly, E, Huang, YCT, Costa, DL, Gilmour, PS & Pinkerton, KE 2006, 'The spontaneously hypertensive rat: An experimental model of sulfur dioxide-induced airways disease', Toxicological Sciences, vol. 94, no. 1, pp. 193-205. https://doi.org/10.1093/toxsci/kfl087
Kodavanti UP, Schladweiler MC, Ledbetter AD, Ortuno RV, Suffia M, Evansky P et al. The spontaneously hypertensive rat: An experimental model of sulfur dioxide-induced airways disease. Toxicological Sciences. 2006 Nov;94(1):193-205. https://doi.org/10.1093/toxsci/kfl087
Kodavanti, Urmila P. ; Schladweiler, Mette C. ; Ledbetter, Allen D. ; Ortuno, Roselia Villalobos ; Suffia, Marie ; Evansky, Paul ; Richards, Judy H. ; Jaskot, Richard H. ; Thomas, Ronald ; Karoly, Edward ; Huang, Yuh Chin T ; Costa, Daniel L. ; Gilmour, Peter S. ; Pinkerton, Kent E. / The spontaneously hypertensive rat : An experimental model of sulfur dioxide-induced airways disease. In: Toxicological Sciences. 2006 ; Vol. 94, No. 1. pp. 193-205.
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