ROS are the principal activators of diabetes-related vascular dysfunction (Brownlee, 2001; Brown and Griendling, 2015; Shah and Brownlee, 2016) and have their effects via a number of intracellular signal transduction pathways (El-Daly et al., 2018), through which they alter the phosphorylation and sensitization of eNOS, and also via the oxidation of BH4 to BH2. Here, NOS3 is linked to diabetes mellitus.