Vitamin E protects against impairment of endothelium-mediated relaxations in cholesterol-fed rabbits.

Abstract

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 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 beta-very-low-density lipoproteins (beta VLDL) isolated from plasma of rabbits fed a cholesterol plus vitamin E diet was almost completely inhibited compared with the oxidation of beta VLDL 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.

Two Patterns of Lipid Deposition in the Cholesterol-Fed Rabbit

“…Evidence obtained with other techniques supports the view that vitamin E protects NO activity in hypercholesterolemia, 19,20,40 but these techniques also have limitations. The measurement of endothelium-dependent relaxation of arteries ex vivo removes the tissue from the chemical, physical, and systemic environment that causes impairment or protection.…”

“…The concentrations of cholesterol and vitamin E and the method for adding them to the diet were based on those used in previous studies demonstrating protection of the NO pathway during hyperlipidemia. 19,20 Plasma lipid levels rose in an identical way in the 2 cholesterol-fed groups (see below), and consequently, there was no requirement for the cholesterol content of the diet to be adjusted during the trial. To obtain disease frequencies similar to those in trial I despite the higher lipid levels, the period of intervention was reduced from 15 to 8 weeks.…”

“…Terminal samples in trial I and pretrial, mid-trial, and terminal samples in trial II were assayed for ␣-tocopherol by high-performance liquid chromatography and the protocol of Stewart-Lee et al 19 with minor modifications. In brief, ethanol, iso-octane, and water were sequentially added to plasma.…”

“…18 Although these effects of cholesterol on wall properties can account for existing data concerning the distribution of experimental atherosclerosis, they are reversible. Quasisteady uptake in adult rabbits returns to its normal pattern during a sustained period of mild hypercholesterolemia, 17 and endothelium-dependent relaxation can be preserved, even in severely hyperlipidemic rabbits, by the administration of vitamin E 19,20 or L-arginine. 21,22 Consequently, if the postulated links between NO activity, transport processes, and disease localization are correct, it should be possible to obtain the upstream distribution of lesions in mature, cholesterol-fed rabbits.…”

Antioxidants, Diabetes, and Endothelial Dysfunction

“…Specifically, vitamin E averted endothelial dysfunction in cholesterol-fed rabbits and streptozotocindiabetic rats. 40,41 However, some studies reported that antioxidant vitamin supplementation may lead to endothelium dysfunction in both diabetic and normal animals. 42,43 Proposed mechanisms for this observation include prooxidant effects of vitamin E on vitamin C in the presence of NO and/or de novo synthesis of vasoconstrictive prostanoids.…”