TY - JOUR
T1 - The spontaneously hypertensive rat
T2 - An experimental model of sulfur dioxide-induced airways disease
AU - Kodavanti, Urmila P.
AU - Schladweiler, Mette C.
AU - Ledbetter, Allen D.
AU - Ortuno, Roselia Villalobos
AU - Suffia, Marie
AU - Evansky, Paul
AU - Richards, Judy H.
AU - Jaskot, Richard H.
AU - Thomas, Ronald
AU - Karoly, Edward
AU - Huang, Yuh Chin T
AU - Costa, Daniel L.
AU - Gilmour, Peter S.
AU - Pinkerton, Kent E
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Bronchitis
KW - Chronic obstructive pulmonary disease
KW - Inflammation
KW - Mucus hypersecretion
KW - Spontaneously hypertensive rats
KW - Sulfur dioxide exposure
UR - http://www.scopus.com/inward/record.url?scp=33749597735&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749597735&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfl087
DO - 10.1093/toxsci/kfl087
M3 - Article
C2 - 16929007
AN - SCOPUS:33749597735
VL - 94
SP - 193
EP - 205
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -