Lipid peroxidation and altered vascular function in vitamin E-deficient rats

Abstract

Female rats deprived of dietary vitamin E for 35 wk postweaning were analyzed for changes in vascular function. A functional state of vitamin E deficiency was indicated by a marked increase in spontaneous hemolysis of washed red cells by 22 wk of feeding. Elevated thiobarbituric acid-reactive material in aorta, liver, and plasma samples from vitamin-E deficient rats indicated increased lipid hydroperoxide formation. Systolic blood pressures and heart rates measured biweekly were unaltered by diet. Before being killed, the rats were catheterized and allowed to recover from anesthesia (methohexital sodium ip). The pressor response to graded doses of angiotensin II was significantly increased in the vitamin E-deficient group relative to its control. Isolated superior mesenteric artery segments from vitamin E-deficient rats demonstrated significantly decreased relaxation responses to acetylcholine. In contrast, artery contractile responses to 50 mM potassium and to graded doses of extracellular calcium did not differ, indicating that contractile capability was maintained. Surface blebbing of the femoral artery endothelium was observed by scanning electron microscopy. These data support a proposed link between lipid peroxidation and development of altered vascular function.

Effects of vitamin E deficiency on vasomotor activity and ultrastructural organisation of rat thoracic aorta

“…However, our results are not in favour of this possibility and rather suggest that a dominant population of al-adrenoceptors located on smooth muscle cells accounts for vascular responses to NA in this tissue. The pharmacological data of the present study confirm and extend our previous observations (Rubino et al, 1993;Rubino & Burnstock, 1994) and are consistent with findings showing that in mesenteric arteries isolated from rats kept on a vitamin E-deficient diet for 8 months, ACh-induced vasodilatation was reduced, while contractile responses to calcium were unaffected (Hubel et al, 1989). In contrast, in mesenteric arteries isolated from rats deprived of dietary vitamin E for only 2 months there was no impairment of the vasodilator response to methacholine (Davidge et al, 1993).…”

“…Our findings are consistent with results obtained in femoral arteries of vitamin E-deficient rats, where a scanning electron micrograph of the endothelial surface showed an irregular endothelial layer. Numerous 'balloon-like projections' into the vascular lumen were also observed (Hubel et al, 1989), which could be compared to the unusual protrusions observed in this study.…”

Combined Deficiency in Glutathione Peroxidase 4 and Vitamin E Causes Multiorgan Thrombus Formation and Early Death in Mice

“…In contrast, rats deprived of dietary vitamin E have been shown to exhibit a decrease in the relaxation response to acetylcholine and elevated MDA serum levels. 35 However, species-specific differences and differences in the composition and duration of the diet (35 instead of 6 weeks) might account for these variations.…”

Effects of vitamin E deficiency on autonomic neuroeffector mechanisms in the rat caecum, vas deferens and urinary bladder.

“…1989), and it has been shown that the cholinergic responses in this vascular bed are endothelium dependent (Ralevic & Burnstock, 1988). Whether the altered responses are due to a damaged endothelium or to a change in receptor binding or transduction was not established (Hubel et al 1989). Furthermore, muscarinic receptors in the rat trachea are susceptible to oxidative stress induced by hydrogen peroxide (Doelman et al 1988), hence it is likely that subsensitive responses to acetylcholine could develop during long-term vitamin E deficiency.…”

“…In rats deficient in vitamin E for 12-24 months there is a large increase in urinary output of catecholamines, especially noradrenaline and adrenaline, which implies a raised level of sympathetic activity (Nakashima & Esashi, 1986, but these animals do not respond to various stressful stimuli with further increased urinary output of catecholamines. Sympathetic control of the cardiovascular system does not appear to be affected by vitamin E deficiency: in vitamin E-deprived rats and monkeys there is no change in resting heart rate or blood pressure (Filer, Rumery, Yu & Mason, 1949;Hubel, Griggs & McLaughlin, 1989). However, the endogenous noradrenaline content of the heart is reduced by up to 50% (Nakashima & Esashi, 1986.…”