Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta

Abstract

We examined the effect in rats of 2 months of streptozotocin-induced diabetes mellitus on relaxation and contraction of aortas in vitro. A further diabetic group was treated from time of diabetes induction with a 1% dietary supplement of vitamin E. Diabetes caused a 26.5% deficit (p < 0.001) in maximum endothelium-dependent relaxation to acetylcholine in phenylephrine-precontracted aortas. This was 64.3% attenuated (p < 0.01) by vitamin E treatment; maximum relaxation was not significantly altered compared to non-diabetic rats. Vitamin E treatment of non-diabetic rats did not significantly affect acetylcholine-induced relaxation. Diabetes or treatment did not significantly alter acetylcholine sensitivity. Endothelium-independent relaxation response to glyceryl trinitrate was not affected by diabetes or vitamin E treatment, indicating that vascular smooth muscle responses to nitric oxide remained unaltered. There was a 35.4% reduction in the maximum contractile response to phenylephrine with diabetes (p < 0.05) which was unaffected by vitamin E treatment. The data suggest that the chronic deficit in nitric oxide-mediated endothelium-dependent relaxation in diabetes depends largely upon excess activity of reactive oxygen species. Treatment with vitamin E to increase free radical scavenging specifically protected vascular endothelium although it had no effect on deficits in vascular smooth muscle contractile responses.

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

“…The well-established tenet that acute hyperglycaemia impairs endothelial function is mainly based on in vitro studies using pharmacological (22 mmol/l or higher) concentrations of glucose [12,13] without insulin or on ex vivo studies using experimental animal models characterised by severe hyperglycaemia [14,15,37,38]. In humans, support for this notion derives mostly from studies using the OGTT as the stimulus, and flow-mediated dilatation of large arteries as the index of endothelial function [23][24][25].…”

“…Experimental evidence indicates that atherogenic mechanisms, such as endothelial dysfunction, oxidative stress and inflammation, may be chronically activated in diabetes [4][5][6][7], at least in part as a consequence of exaggerated postprandial glucose excursions [8][9][10]. The negative impact of hyperglycaemia-induced oxidative stress on endothelial dysfunction has been reported in a number of in vitro and animal studies [11][12][13][14][15]. Most of these studies, however, have applied rather extreme experimental conditions, making it difficult to assess their relevance either to diabetes, or to impaired glucose tolerance (IGT) where glucose excursions are smaller, smoother and associated with various degrees of hyperinsulinaemia.…”

Endothelial dysfunction in diabetes

“…Acute administration of scavengers of superoxide anion, including superoxide dismutase (Hattori et al, 1991;Tesfamariam & Cohen, 1992;Pieper et al, 1996;Bohlen & Lash, 1993) and the combination of superoxide dismutase with catalase (Pieper et al, 1997) improved or normalized the abnormal endothelium-dependent responses in di erent models of diabetes and during high glucose exposure. Similarly, chronic treatment with probucol (Tesfamariam & Cohen, 1992), N-acetylcysteine (Pieper & Siebeneich, 1998b), vitamin E (Keegan et al, 1995;RoÈ sen et al, 1996) and vitamin C (Ting et al, 1996) prevented the development of endothelial dysfunction in clinical and experimental diabetes. In an in vivo study of high glucose exposure of the mesenteric circulation, superoxide dismutase and catalase were equally or more e ective than cyclo-oxygenase inhibition in restoring the impaired ACh-induced vasodilatation, suggesting that the oxygen-derived radicals produced during prostanoid synthesis, rather than the prostanoids themselves, were responsible for the endothelial dysfunction (Bohlen & Lash, 1993).…”

Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model

“…29,30 Vitamin E has also been reported to improve NO-mediated arterial relaxation, maintain cell membrane integrity and protein stability. 31,32 The potential impact of combining vitamin E and sildenafil to treat diabetes induced ED (ED-DM) remains to be determined. This animal study was designed to gain insight into the potential clinical utility of this approach.…”