A High-fat, Refined-Carbohydrate Diet Induces ...

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A High-fat, Refined-Carbohydrate Diet Induces Endothelial

Dysfunction, Oxidant/Antioxidant Imbalance and Depresses NOS Protein

Expression.

CK, Barnard RJ, Sindhu RK, Jurczak M, Ehdaie A, Vaziri ND.

Department of Physiological Science, University of California, Los

Angeles, Los Angeles, CA, USA.

J Appl Physiol. 2004 Aug 27

We tested whether consumption of a high-fat, high-sucrose (HFS) diet

can affect endothelium-dependent relaxation, if this precedes the

development of diet-induced hypertension previously noted in this

model, and if it is mediated, in part, by changes in nitric oxide

synthase (NOS) and/or NOS regulatory proteins. Female Fischer rats

were fed either a HFS diet or standard low-fat, complex-carbohydrate

(LFCC) chow starting at 2 months of age for 7 months.

Vasoconstrictive response to KCl and phenylephrine was similar in

both groups. Vasorelaxation to acetylcholine was significantly

impaired in the HFS animals and there were no differences in

relaxation to sodium nitroprusside, suggesting that the endothelial

dysfunction is due, at least in part, to NO deficiency. HFS

consumption decreased protein expression of endothelial NOS in aorta,

renal and heart tissues, neuronal NOS in kidney, heart, aorta and

brain and inducible NOS in heart and aorta. Caveolin-1 (Cav-1) and

soluble guanylate cyclase (sGC-beta) protein expression did not

change, but AKT protein expression decreased in heart and aorta and

increased in kidney tissue. Consumption of HFS diet raised brain

carbonyl content and plasma hydrogen peroxide concentration and

diminished plasma total antioxidant capacity. Since blood pressure,

which is known to eventually rise in this model, was not as yet

significantly elevated, the present data suggest that endothelial

dysfunction precedes the onset of diet-induced hypertension. The lack

of quantitative change in Cav-1 and sGC-beta protein content

indicates that alteration in these proteins is not responsible for

the endothelial dysfunction. Thus, NO deficiency, combined with

antioxidant/oxidant imbalance, appear to be primary factors in the

development of endothelial dysfunction in this model.