Our data show by the first time that in the 2K1C angiotensin II-dependent hypertension, the protective actions of sildenafil are not solely mediated through a reduction in the known molecular mechanisms of oxidative stress, but also through other pathways, including the reduction of intrarenal angiotensin II levels and, thus, contributing to attenuation of NADPH oxidase signaling [17,41]. Here, FMO5 is linked to substance dependence.