NOS3 and endothelial dysfunction: In cardiovascular diseases, eNOS-associated endothelial dysfunction may result from (a) increased endothelial O2− production through an NAD(P)H oxidase-dependent mechanism, (b) increased ONOO− synthesis, (c) decreased endothelial BH4 bioavailability, and (d) a metabolic syndrome-related pro-inflammatory state (53–57).