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Pulmonary Complications Resulting from Genetic Cardiovascular Disease in Two Rat Models
Citation:
SHANNAHAN, J. H., A. D. LEDBETTER, M. SCHLADWEILER, A. J. GHIO, AND U. P. KODAVANTI. Pulmonary Complications Resulting from Genetic Cardiovascular Disease in Two Rat Models . Presented at Annual Society of Toxicology meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This abstract characterizes baseline pulmonary inflammation, oxidative stress and iron homeostasis dysregulation in two rat models of cardiovascular disease relative to healthy rats.
Description:
Underlying cardiovascular disease (CVD) has been considered a risk factor for exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Pulmonary complications and altered iron homeostasis secondary to CVD may influence outcomes of air pollution exposure. In this study we characterized baseline pulmonary endpoints of iron homeostasis, oxidative stress, and inflammation in rat models of CVD. Healthy normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SH), and the spontaneously hypertensive heart failure (SHHF) rats were evaluated at 11-14 wk old. Blood pressure and heart rate measurements taken by tail cuff were increased in SH and SHHF rats relative to WKY rats (SHR>SHHF>WKY). Breathing parameters measured using whole body plethysmography demonstrated increases in breathing frequency and tidal volume resulting in increased minute volume in SHHF and SH relative to WKY rats (SHR>SHHF>WKY). High blood pressure was correlated with increased minute volume. BALF protein and neutrophils were increased in SHHF and SH relative to WKY rats (SHHF>>SH>WKY). Real-time RT-PCR indicated differences in markers of inflammation and oxidative stress in lungs among strains. Pulmonary MIP-2, IL-1α, and HO-1 expressions were greater in SHHF and SHR relative to WKY. Affymetrix gene array data demonstrated alterations of several genes related to heme metabolism in lungs of SHHF but not SH rats when compared to WKY. BALF non-heme iron was also increased in SHHF relative to WKY and was associated with increases in transferrin and ferritin. This study demonstrates that SHHF have greater pulmonary complications of oxidative stress, inflammation and altered iron homeostasis than WKY or SH rats which may play a role in their increased susceptibility to air pollution. Funded by EPA/UNC CR833237 (This abstract does not reflect US EPA policy)