Strain differences in antioxidants in rat models of cardiovascular disease exposed to ozone

Abstract

We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to O₃ in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF), insulin-resistant JCR:LA-cp obese (JCR) and Fawn-Hooded hypertensive (FHH)] were compared with normal strains [Wistar, Sprague–Dawley (SD) and Wistar Kyoto (WKY)]. Total glutathione (GSH + GSSG or GSx), reduced ascorbate (AH2), uric acid (UA) and antioxidant enzymes were determined in lung, heart and BALF immediately (0 h) or 20-h post 4-h nose-only exposure to 0.0, 0.25, 0.5 and 1.0 ppm O₃. Basal- and O₃-induced antioxidant substances in tissues varied widely among strains. Wistar rats had a robust O₃-induced increase in GSx and AH2 in the lung. Two CVD strains (JCR and SHHF) had high basal levels of AH2 and GSx in BALF as well as high basal lung UA. Across all strains, high BALF GSx was only observed when high BALF AH2 was present. CVD rats tended to respond less to O₃ than normal. High-basal BALF AH2 levels were associated with decreased O₃ toxicity. In summary, large differences were observed between both normal and CVD rat strains in low-molecular weight antioxidant concentrations in lung, BALF and heart tissue. Wistar (normal) and JCR and SHHF (CVD) rats appeared to stand out as peculiar in terms of basal- or O₃-induced changes. Results elucidate interactions among antioxidants and air pollutants that could enhance understanding of cardiopulmonary disease.

• Cardiovascular disease models
• lung antioxidants
• oxidative stress
• ozone
• rat models

Acknowledgements

We thank Drs. Daniel L. Costa, Barbara Buckley and Andrew Ghio of the U.S. EPA and Dr. Maria Kadiiska of the National Institute of Environmental Health Sciences, NIH for internal review of the manuscript.

Declaration of interest

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.