Model for regulation of ARH activity. We propose that ARH exists in three states: a free sulfhydryl state, a nitrosylated state, and a disulfide-bonded state. The free sulfhydryl form can react with nitric oxide produced by NOS enzymes to generate the active, nitrosylated form of ARH. Nitrosylation catalyzes disulfide bond formation, leading to inactivation of ARH. Cytosolic reductases (e−) reduce disulfide-bonded ARH to the free sulfhydryl form. Active ARH is presented as a hexagon, and inactive ARH is presented as a square.