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International Journal of Hypertension
Volume 2012, Article ID 740203, 11 pages
Research Article

Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

1Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, Japan
2Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH, 43614, USA
3Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
4Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy
5Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA

Received 12 August 2011; Accepted 19 September 2011

Academic Editor: David E. Stec

Copyright © 2012 Tomoko Kawakami et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression; although, HO activity was significantly ( ) attenuated along with attenuation of serum adiponectin and vascular epoxide levels ( ). CoPP, in EC-SOD(−/−) mice, enhanced HO activity ( ) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−) mice.