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Pulmonary oxidative stress, inflammation and dysregulated iron homeostatis in rat models of cardiovascular disease
Shannahan, J., M. SCHLADWEILER, J. E. Richards, AND A. J. GHIO. Pulmonary oxidative stress, inflammation and dysregulated iron homeostatis in rat models of cardiovascular disease. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 73(10):641-656, (2010).
Animals models of cardiovascular diseases are extensively used to understand susceptibility to air polltuion health effects. This study provides the data on pulmonary complications associated with cardiac dieases in animal models that can influence their susceptibility to air pollution-induced health effects. D
Underlying cardiovascular disease (CVD) is considered a risk factor for the exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms ofvariation in susceptibility. Pulmonary oxidative stress, inflammation and altered iron homeostasis secondary to CVD may influence outcomes of air pollution exposure. We characterized these baseline pulmonary complications in healthy normotensive Wistar Kyoto (WKY), and cardiovascular compromised spontaneously hypertensive (SH), and spontaneously hypertensive heart failure (SHHF) rats at 14-15 wk of age. Blood pressure and heart rate were increased in SH and SHHF relative to WKY (SHR>SHHF>WKY). Increased breathing frequency in SHHF and SH (SHR>SHHF>WKY) resulted in greater minute volume relative to WKY. Bronchoalveolar lavage fluid (BALF) protein and neutrophils were increased in SHHF and SH relative to WKY (SHHF»SH>WKY). Lung ascorbate and glutathione were low in SHHF rats. BALF iron-binding capacity was decreased in SHHF relative to WKY and was associated with increased Trf and ferritin. However, lung ferritin was lower and Trfwas higher in SHHF relative to WKY or SH. mRNA for markers of inflammation and oxidative stress (MIP-2, IL-la, and HO-l) were greater in SHHF and SH relative to WKY. Trf mRNA increased in SH but not in SHHF relative to WKY, whereas transferrin receptors 1 and 2 mRNA were lower in SHHF. Four of 12 WKY rats exhibited cardiac hypertrophy despite normal blood pressure, while demonstrating some of the pulmonary complications noted above. This study demonstrates that SHHF have greater underlying pulmonary complications of oxidative stress, inflammation and impaired iron homeostasis than WKY or SH rats which may playa role in their increased susceptibility to air pollution. 3 Disclaimer: The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and neither the policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. .
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH