The available data obtained in animal models identified several mechanisms of ED: decreased endothelial NO production, excessive endothelial O2– production, deficiency in the NOS cofactor BH4, upregulation of arginase, upregulation of NADP (H) oxidase, and overactivation of COX-2, TX synthase, and PGI2 synthase, thereby identifying future potential targets for new therapeutic options to treat ED in patients with arthritis. The gene discussed is NOS2; the disease is arthritic joint disease.