Endothelial Nitric Oxide Synthase Uncoupling And Oxidative Stress

Endothelial dysfunction is the common pathological base for a number of cardiovascular diseases. Reduction of NO bioavailability and excessive generation of reactive oxygen species (ROS) are key factors which cause endothelial dysfunction. Endothelial nitric oxide synthase uncoupling (eNOS- uncoupling) is an important mechanism underlying the pathological phenomenon of reduced NO production and enhanced free radicals generation. Higher level of ROS is the major cause of eNOS-uncoupling which exerts influence on protein structure, co-factor as well as the substrate of eNOS. Furthermore, the dual effects of ROS also attract the attention: on the one hand, ROS react with biological macromolecules such as proteins, lipids, nucleic acids, which results a number of pathological consequences. On the other hand, ROS is necessary for certain physiological signaling. The compartmental effects of ROS should be responsible for above phenomenon. Inhibition of ROS in specific region may open up novel pathway for the prevention and treatment of cardiovascular diseases through the means of blocking key ROS synthesis enzymes; preventing and reversing eNOS uncoupling, and improving endothelial function.