In this study, hyperglycemia decreased BH4 levels via inhibition of 26S proteasome activity of guanosine 5'-triphosphate cyclohydrolase I (GTPCH), which is a rate-limiting enzyme of BH4 synthesis, and increased levels of peroxynitrite, which oxidizes BH4 to dihydrobiopterin (BH2), thereby uncoupling eNOS (Xu et al., 2007). This evidence concerns the gene NOS3 and Hyperglycemia.