The Significance of NO-Synthase, Reactive Oxygen Species, Kinases and KATP-Channels in the Development of the Infarct-Limiting Effect of Adaptation to Hypoxia

The cardioprotective effect of chronic hypoxia (CH) is associated with the activation of inducible nitric oxide synthase (iNOS). Reactive oxygen species (ROS) are involved in the development of CH-induced cardiac tolerance to ischemia/reperfusion. The infarct-limiting effect of CH depends on the opening of mitochondrial ATP-sensitive potassium (mitoK ATP ) channels. Protein kinase C δ and ε isoforms are involved in the cardioprotective effect of adaptation to hypoxia. CH increases the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), phosphorylated p38 (p-p38), phosphorylated AMP-activated protein kinase (p-AMPK), as well as hexokinase-1 (HK1) and hexokinase-2 (HK2). ERK1/2 and mitogen-activated protein kinases (MEK1/2) are involved in the cardioprotective effect of adaptation to hypoxia. The role of atrial natriuretic peptide (ANP), erythropoietin, endothelin-1, phosphoinositide 3-kinases (PI3K), protein kinase G (PKG), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) in the protective effect of adaptation to hypoxia requires further research.