A high-fat, refined-carbohydrate diet induces endothelial dysfunction and oxidant/antioxidant imbalance and depresses NOS protein expression.

We tested whether consumption of a high-fat, high-sucrose (HFS) diet can affect endothelium-dependent relaxation, whether this precedes the development of diet-induced hypertension previously noted in this model, and whether 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 chow starting at 2 mo of age for 7 mo. 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 nitric oxide 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 and soluble guanylate cyclase 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. Because 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 a quantitative change in caveolin-1 and soluble guanylate cyclase protein content indicates that alteration in these proteins is not responsible for the endothelial dysfunction. Thus nitric oxide deficiency combined with antioxidant/oxidant imbalance, appears to be a primary factor in the development of endothelial dysfunction in this model.     

The role of water structure in conformational changes of nucleic acids in ambient and high-pressure conditions.

This review describes and summarizes data on the structure and properties of water under normal conditions, at high salt concentration and under high pressure. We correlate the observed conformational changes in nucleic acids with changes in water structure and activity, and suggest a mechanism of conformational transitions of nucleic acids which accounts for changes in the water structure. From the biophysical, biochemical and crystallographic data we conclude that the Z-DNA form can be induced only at low water activity produced by high salt concentrations or high pressure, and accompanied by the stabilizing conjugative effect of the cytidine O4' electrons of the CG base pairs.