Submitted on November 22, 2006
Accepted on March 26, 2007
Dynamic Changes in Nitric Oxide and Mitochondrial Oxidative Stress with Site-Dependent Differential Tissue Response during Anoxic Preconditioning in Rat Heart
Dang Van Cuong1, Nari Kim1, Mohamad Warda1, Won Sun Park2, Jae-Hong Ko2, Euiyong Kim1, and Jin Han2*
1 Department of Physiology and Biophysics, College of Medicine, Inje University, Busan, Korea, Republic of
2 Busan, Korea, Republic of; Department of Physiology and Biophysics, College of Medicine, Inje University, Busan, Korea, Republic of
* To whom correspondence should be addressed. E-mail: Phyhanj{at}inje.ac.kr.
In this study, dynamic changes in NO and mitochondrial superoxide (O2-.) were examined during anoxic preconditioning in rat heart model. Anoxic preconditioning (AP) and anoxia-reoxygenation (A/R) were performed on isolated hearts and single cardiomyocytes. The cellular insult in the form of infarct size and DNA damage were localized and correlated with NO synthases (endothelial and inducible) expression levels. The results showed that endocardium was the most affected region in AP groups, whilst the larger area of infarct was confined to epicardium in the A/R group. Interestingly, high-level expression of immunofluorescent NO synthases was restricted to viable areas in the AP. In contrast to gradual increase in O2-. level that occurred in the AP group, a sudden massive increase in its level was demonstrated at the onset of reperfusion in the A/R group. The observed increase in NO production during reperfusion in AP group was attenuated by inducible NOS inhibitor. The study revealed, on real-time basis, the role played by preconditioning for modulating NO and O2-.. levels on behalf of cell survival. The results afford a better understanding of cardiac adapting mechanism during anoxic preconditioning and the role of iNOS in this important phenomenon.
