Moreover, when in hypertension or atherosclerosis eNOS was uncoupled to produce superoxide rather than NO (Landmesser et al., 2003), endothelial NOX4-derived H2O2 could mediate compensatory relaxation acting as an endothelium-derived hyperpolarizing factor (Yada et al., 2003). Here, NOS3 is linked to hypertensive disorder.