ROS and NO trigger early preconditioning: relationship to mitochondrial K ATP channel

作者：Gilles Lebuffe, Paul T. Schumacker, Zuo‐Hui Shao, Travis Anderson, Hirotoro Iwase, Terry L. Vanden Hoek · 发表于：American Journal of Physiology-Heart and Circulatory Physiology · 年份：2003 · DOI：10.1152/ajpheart.00706.2002 · 被引用次数：225 · 研究领域：Cardiac Ischemia and Reperfusion、Cardiac Arrest and Resuscitation、Anesthesia and Neurotoxicity Research

Reactive oxygen species (ROS) and nitric oxide (NO) are implicated in induction of ischemic preconditioning. However, the relationship between these oxidant signals and opening of the mitochondrial ATP-dependent potassium (K(ATP)) channel during early preconditioning is not fully understood. We observed preconditioning protection by hypoxia, exogenous H(2)O(2), or PKC activator PMA in cardiomyocytes subjected to 1-h ischemia and 3-h reperfusion. Protection was abolished by K(ATP) channel blocker 5-hydroxydecanoate (5-HD) in each case, indicating that these triggers must act upstream from the K(ATP) channel. Inhibitors of NO synthase abolished protection in preconditioned cells, suggesting that NO is also required for protection. DAF-2 fluorescence (NO sensitive) increased during hypoxic triggering. This was amplified by pinacidil and inhibited by 5-HD, indicating that NO is generated subsequent to K(ATP) channel activation. Exogenous NO during the triggering phase conferred protection blocked by 5-HD. Exogenous NO also restored protection abolished by 5-HD or N(omega)-nitro-l-arginine methyl ester in preconditioned cells. Antioxidants given during pinacidil or NO triggering abolished protection, confirming that ROS are generated by K(ATP) channel activation. Coadministration of H(2)O(2) and NO restored PMA-induced protection in 5-HD-treated cells, indicating that ROS and NO are required downstream from the K(ATP) channel. We conclude that ROS can trigger preconditioning by ca...