THE ANTIOXIDANT BUTYLATED HYDROXYTOLUENE PREVENTS EARLY CHOLESTEROL-INDUCED MICROCIRCULATORY CHANGES IN RABBITS

Microcirculation was studied during 10 wk in untreated rabbits (n = 13 ) and in rabbits treated with dietary addition of 1% cholesterol (n = 13), 1% cholesterol + 1% of the antioxidant BHT (butylated hydroxytolu ene) (n = 11), or 1% BHT (n = 5). The studies were performed by direct intravital microscopic imaging of the left and right conjunctivae wit h the use of a stereo microscope and a high resolution television came ra. Microvessel diameter, erythrocyte flow velocity, and microhemorheo logic conditions were evaluated quantitatively via a computer-assisted digital image processing system. Significant and marked changes occur red in all the above variables as a consequence of cholesterol feeding . After 3 wk of feeding there was a dramatic decrease(similar to 30%) in blood now velocity in arterioli of the third order (P < 0.0001), ac companied by aggregation of cells in 40-50% of the smaller conjunctiva l vessels (P < 0.0001). These changes were enhanced further during the following 7 wk of treatment. All the above changes in the microcircul ation were markedly reduced by the addition of BHT treatment. The diam eter of the above arterioli decreased in the purely cholesterol-fed gr oup (P < 0.005), whereas this did not occur in the group fed both chol esterol and BHT. In rabbits fed BHT in the absence of cholesterol, the re was no significant effect on any assessed microcirculatory variable . In conclusion, the results demonstrate that the antioxidant BHT prev ented early cholesterol-induced microcirculatory changes. This prevent ion occurred in the absence of a reduction of blood lipid levels. The results provide strong support for the hypothesis that a considerable part of the effects on microcirculation in hypercholesterolemia mag be due to cholesterol-induced oxidations and not to cholesterol itself. The results are discussed in relation to the previously demonstrated a ntiatherogenic effect of BHT and the possible use of antioxidants in t he therapy and prophylaxis of atherosclerosis.