Constant hyperglycemia inhibits the enzyme eNOS (endothelial nitric oxide synthase) and thus cause the reduction of nitric oxide and the stimulation of the production of reactive oxygen species, including superoxide anion (O2−) [48]; superoxide anion neutralizes nitric oxide by producing the toxic ion peroxynitrite, which uncouples the eNOS enzyme by oxidizing its cofactor, tetrahydrobiopterin [49]. The gene discussed is NOS3; the disease is Hyperglycemia.