eNOS uncoupling occurs through the following mechanisms: (1) deficiency of the cofactor tetrahydrobiopterin through its oxidation by peroxynitrite or (2) deficiency of the substrate L-arginine attributed to increased arginase expression observed in hypertension [24–27], and (3) S-glutathionylation observed in angiotensin II-induced hypertension [28]. The gene discussed is AGT; the disease is hypertensive disorder.