Tocomin Attenuates Oxidative Stress and Improves NO Mediated Relaxation in Aortaefrom Rats Fed a High Fat Diet

We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. We investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high fat diet. Wistar hooded rats were fed a western diet (WD, 21% fat) or control rat chow (SD, 6% fat) for 12 weeks. Tocomin (40 mg/kg/day sc) or its vehicle was administered for the last 4 weeks of feeding. Aortae from WD rats showed an impairment of endothelium-dependent relaxation that was associated with an increased expression of the NADPH oxidase Nox2 subunit and an increase in the generation of superoxide. The increase in vascular oxidative stress was accompanied by a decrease in basal NO release and impairment of the contribution of NO to ACh-induced relaxation. The impaired relaxation is likely contributed to by a decreased expression of eNOS, calmodulin and phosphorylated Akt and an increase in caveolin. Tocomin prevented the diet-induced changes in vascular function, reduced vascular superoxide production and abolished the diet-induced changes in eNOS and other protein expression. Using selective inhibitors of nitric oxide synthase (NOS), soluble guanylate cyclase (sGC) and calcium activated potassium (K Ca ) channels we demonstrated that tocomin selectively increased NO mediated relaxation. The beneficial actions of tocomin suggests that it may have potential to be used as a therapeutic agent to prevent vascular disease in obesity.