NOS3 and hyperlipidemia: Possible mechanisms underlying hyperlipidaemia-induced ED include: (1) upregulation of NADPH oxidase, increased O2– production and oxidative stress, (2) increased plasma levels of asymmetric dimethylarginine (ADMA),25 and (3) oxidation of LDL.27 ADMA is an endogenous inhibitor of eNOS and competes with L-arginine for the same binding site on eNOS, thus resulting in eNOS uncoupling, increased O2– production and hence decreased NO production.