Endothelium-Mediated Relaxations in Cholesterol-Fed Rabbits

The vascular effects of dietary vitamin E were investigated in isolated carotid artery preparations from cholesterol-fed New Zealand White rabbits. Rabbits were fed either a control, 1% cholesterol, or 1% cholesterol plus 0.2% vitamin E diet for 4 weeks. In raised-tone preparations, relaxant responses to acetylcholine were enhanced in rabbits fed cholesterol plus vitamin E, reversing the reduction in responses measured in preparations from cholesterol-fed rabbits. Relaxant responses to the calcium ionophore A23187 were significantly enhanced in cholesterol plus vitamin E-fed rabbits compared with those fed cholesterol alone, with no difference between control and cholesterol-fed rabbits. Relaxant responses to sodium nitroprusside were not different between the three dietary groups. Constrictor responses to Hypercholesterolemia induces endothelial dysfunction, leading to an impairment of endothelium-mediated relaxant responses. ~ This may be a result of an attenuation in the production, release, or bioactivity of nitric oxide-related endothelium-derived relaxing factor (EDRF). Reactive oxygen species (ROS) are known to be released from monocytes/intimal macrophages, smooth muscle cells, endothelial cells, and LDL during its modification in the arterial wall, and it is possible that they contribute to endothelial dysfunction, since ROS generation is increased in atherosclerotic vesselsand there is evidence that ROS inactivate EDRF in vitro. Vitamin E is the most abundant, naturally occurring, lipid-soluble antioxidant in plasma. It is carried within the low-density lipoprotein (LDL) particle and prevents its oxidation in vitro. Low doses of vitamin E (0.2%) do not have a significant effect on plasma cholesterol levels; therefore, a 1% cholesterol diet containing 0.2% vitamin E could be used to test its action as an antioxidant agent in a model of atherogenesis. In the present study, we have examined the possible role of oxidative processes in the early impairment of endothelium-mediated responses by studying the effects of the antioxidant vitamin E on endothelium-mediated relaxations in the carotid artery of the hypercholesterolemic rabbit. Received June 24, 1993; revision accepted December 14, 1993. From The William Harvey Research Institute, St Bartholomew's Hospital Medical College, University of London, UK. Correspondence to Dr A.L. Stewart-Lee, The William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UK. noradrenaline and serotonin in isolated carotid artery preparations at basal tone were unaltered after cholesterol and cholesterol plus vitamin E diets. The copper-induced oxidation of /3-very-low-density lipoprotein (/3VLDL) isolated from plasma of rabbits fed a cholesterol plus vitamin E diet was almost completely inhibited compared with the oxidation of /3VLDL from rabbits fed cholesterol alone. These results show that vitamin E prevents endothelial dysfunction associated with cholesterol feeding and suggests that vitamin E may be beneficial in preventing functional impairment associated with atherosclerosis. (Arterioscler Thromb. 1994;14:494-499.)