NOS3 and endothelial dysfunction: Hyperglycemia determines endothelial dysfunction through multiple pathways such as the activation of nuclear factor (NF)-κB, which increases the expression of inducible nitric oxide synthase (iNOS) and increased generation of NO, decreased activity of endothelial nitric oxide synthase (eNOS) and enhanced mitochondrial production of the superoxide anion radicals, increased degradation of NO through its reaction with superoxide and formation of peroxynitrite [11,12,13,14].