Cardioprotective strategies to prevent damage to mitochondria in acute myocardial infarction are warranted to reduce lethal myocardial ischemia/reperfusion (I/R) injury. Mitochondrial antagonists in I/R are reactive oxygen species (ROS), deteriorated calcium signaling, permeabilization of the mitochondrial outer membrane (MOM) and deranged mitochondrial structural dynamism (fusion and fission). Nitric oxide (NO) related signaling can protect hearts from I/R. Albeit the underlying signaling is incompletely resolved, recent data point to a particular involvement of protective posttranslational modification of mitochondrial elements. We and others have demonstrated that hypoxic NO signaling in cardiomyocytes is associated with a posttranslational mitochondrial complex I modification to reduce the burden of ROS. Induction of cardioprotective NO signaling may occur through several pathways. These include (i) the supplementation with mitochondria unspecific and specific NO-donors, (ii) the administration of the 'hypoxic-NO donors nitrate and nitrite' and (iii) the enhancement of endogenous NO formation, e.g. by remote ischemic preconditioning maneuvers (rIPC). In this chapter, we outline how NO signaling is activated in the cardiomyocyte, characterize the downstream signaling pathways and discuss how this could translate into a tractable therapeutic approach in patients requiring cardioprotection.
Keywords: Ischemia/reperfusion injury; NO Donor; Nitrate; Nitric oxide; Nitrite; S-nitrosation.