Cholesterolinduced changes in macro- and microvessels in rabbits : effects of antioxidants

Abstract

A hyperlipidemic state induced by cholesterol feeding results in changes in both the structure and function of macro- and microvessels in rabbits. It has been proposed that oxidative modification of lipoproteins might be an important pathophysiological mechanism explaining these effects of hyperlipidemia. This contention has been supported by a number of in vitro studies. The aim of the present study was to investigate whether the use of antioxidants in vivo in a rabbit model interferes with some of the changes induced in vessels by cholesterol feeding.

Studies with butylated hydroxytoluene (BHT) demonstrated that this lipophilic anti oxidant had an inhibitory effect on the formation of macroscopic lesions in the thoracic aorta of cholesterol fed New Zealand White rabbits. This effect was present without any decrease in serum levels of cholesterol, triglycerides or high density lipoprotein (HDL). There was a significant correlation between the inhibitory effect of BHT on the extent of aortic lesions and a rise in triglycerides.

Furthermore, BHT treatment had a significant inhibitory effect on the resulting intimal aortic lesions after balloon injury of the thoracic aorta combined with a more moderately cholesterol enriched diet in rabbits. In addition, feeding rabbits a cholesterol enriched diet induced marked changes in the microcirculation in their conjunctivae as demonstrated by in vivo microscopy. BHT treatment counteracted several of the microcirculatory changes induced by the cholesterol diet; more specifically the reduction in blood flow velocity and arteriolar diameter as well as the occurrence of aggregation, stasis and segmental dilations in the microcirculatory vessels.

Studies with the aqueous antioxidant ascorbate added to the drinking water did not inhibit the development of macroscopic lesions in the thoracic aorta of cholesterol fed New Zealand White rabbits. In contrast, treatment with ascorbate had significant effects in counteracting some of the microcirculatory effects observed with cholesterol feeding such as reduction in blood flow velocity and the occurrence of aggregation and stasis.

The lipophilic antioxidant BHT is shown to interfere with three different processes of interest for the understanding of the development of atherosclerosis. The findings in this study are consistent with the oxidation hypothesis. We cannot exclude the possibility however, that the effect is unrelated to the antioxidant properties of BHT. The preventive effect of both BHT and the aqueous antioxidant ascorbate on changes in the microcirculation induced by dietary cholesterol, provides strong support for the contention that oxidative reactions are of importance for regulation of the microcirculation. However, whether or not oxidized lipoproteins are involved in this regulation remains to be established. The possibility is discussed, that antioxidants may prove useful in the prevention of microcirculatory dysfunction.