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Nitric oxide is an important endogenously made vasodilator that has numerous antiatherosclerotic properties. Many lines of evidence suggest that a lack of nitric oxide can lead to hypertension and atherosclerotic plaque formation.1 Nitric oxide synthase (NOS) is the enzyme that produces nitric oxide in the body. The two main inhibitors of NOS are asymmetric dimethyl arginine (ADMA) and NG-monomethyl arginine. These NOS inhibitors are metabolised and inactivated by the enzyme dimethyarginine dimethylamine hydrolase (DDAH). Thus, inhibition of DDAH can lead to a reduction in NOS.
The oxidation of the omega-6 fat linoleic acid can form the highly reactive aldehyde called 4-hydroxy-2-nonenal (4-HNE), which has been noted to reduce nitric oxide generation from endothelial cells by reducing the activity of the DDAH enzyme.2 An inhibition of DDAH increases the NOS inhibitor ADMA in endothelial cells causing endothelial NOS (eNOS) ‘uncoupling’ and increased production of superoxide rather than nitric oxide. Since ADMA competitively inhibits NOS and is an independent cardiovascular risk factor this suggests that consuming isolated forms of linoleic acid, such as refined omega-6 vegetable oils, may lead to elevations in blood pressure and potentially hypertension.3 Moreover, linoleic acid inhibits insulin signalling and eNOS activation in the vasculature both of which are implicated in hypertension.4
Conditions with reduced NOS activity coincide with disease states that are hallmarked by an increase in oxidised lipids, including oxidised linoleic acid. When LDL becomes oxidised, this is initially from the oxidised linoleic acid contained within the LDL, which forms the highly reactive aldehyde 4-HNE, levels of which coincide with increased atherosclerotic progression.2 Since oxidised LDL is found in atherosclerotic lesions in animals and in humans5 and can directly cause endothelial dysfunction via reductions in nitric oxide, the ability of dietary linoleic acid to increase LDL susceptibility to oxidation suggests …