Unlike NOX4, NOX5 produces superoxide, which can either uncouple endothelial NOS in hypertension by oxidation of H4Bip [85, 86] in a sepiapterin-reversible manner [87] or scavenge NO to form peroxynitrite, which may also act as a cytotoxic agent or vasodilator [88, 89]. This evidence concerns the gene NOX4 and hypertensive disorder.