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Erschienen in: Diabetologia 6/2004

01.06.2004 | Article

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

verfasst von: S. J. Wigg, M. Tare, J. Forbes, M. E. Cooper, M. C. Thomas, H. A. Coleman, H. C. Parkington, R. C. O’Brien

Erschienen in: Diabetologia | Ausgabe 6/2004

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Abstract

Aims/hypothesis

The impact of early vitamin E supplementation on vascular function in diabetes remains unresolved. Therefore, we examined the effects of vitamin E on functional and structural parameters and on chemical markers that are disturbed in diabetes in mesenteric and femoral arteries.

Methods

Segments of both arteries, taken from control and 8-week-old streptozotocin diabetic Wistar rats that were treated or not with vitamin E, were mounted on wire and pressure myographs, after which endothelium-dependent and -independent vasodilation was assessed. Passive mechanical wall properties and the localisation and levels of protein kinase C (PKC)-β2 and AGE were evaluated in these vessels.

Results

Vitamin E supplementation was associated with improved endothelium-dependent and -independent vasodilatation in mesenteric arteries from diabetic rats. Impaired endothelium-dependent vasodilatation in diabetic mesenteric vessels was associated with PKC-β2 up-regulation and this was prevented by vitamin E supplementation. Increased AGE accumulation and plasma isoprostane levels in diabetic rats were not changed by vitamin E. In the femoral artery, vitamin E supplementation had no effect on endothelium-dependent or -independent vasodilatation, but did prevent the wall stiffening associated with diabetes.

Conclusions/interpretation

Early vitamin E supplementation has a beneficial effect on diabetes-induced endothelial dysfunction in resistance arteries. This benefit may arise from a direct effect on smooth muscle function, as a result of inhibition of the PKC-β2 isoform by vitamin E.
Literatur
1.
Zurück zum Zitat Feener EP, King GL (1997) Vascular dysfunction in diabetes mellitus. Lancet 350:SI9–SI13PubMed Feener EP, King GL (1997) Vascular dysfunction in diabetes mellitus. Lancet 350:SI9–SI13PubMed
2.
Zurück zum Zitat De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM (2000) Endothelial dysfunction in diabetes. Br J Pharmacol 130:963–974PubMed De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM (2000) Endothelial dysfunction in diabetes. Br J Pharmacol 130:963–974PubMed
3.
Zurück zum Zitat Andrews HE, Brukdorfer KR, Dunn RC, Jacobs M (1987) Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta. Nature 327:237–239CrossRefPubMed Andrews HE, Brukdorfer KR, Dunn RC, Jacobs M (1987) Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta. Nature 327:237–239CrossRefPubMed
4.
Zurück zum Zitat Yasunari K, Kohno M, Kano H, Yokokawa K, Minami M, Yoshikawa J (1999) Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose. Circulation 99:1370–1378PubMed Yasunari K, Kohno M, Kano H, Yokokawa K, Minami M, Yoshikawa J (1999) Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose. Circulation 99:1370–1378PubMed
5.
Zurück zum Zitat Wolffenbuttel BHR, Boulanger CM, Crijns FRL et al. (1998) Breakers of advanced glycation end-products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 95:4630–4634PubMed Wolffenbuttel BHR, Boulanger CM, Crijns FRL et al. (1998) Breakers of advanced glycation end-products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 95:4630–4634PubMed
6.
Zurück zum Zitat Kunisaki M, Fumio U, Nawata H, King GL (1996) Vitamin E normalizes diacylglycerol—protein kinase C activation induced by hyperglycaemia in rat vascular tissues. Diabetes 45 [Suppl 3]:S117–S119 Kunisaki M, Fumio U, Nawata H, King GL (1996) Vitamin E normalizes diacylglycerol—protein kinase C activation induced by hyperglycaemia in rat vascular tissues. Diabetes 45 [Suppl 3]:S117–S119
7.
Zurück zum Zitat Sugiyama S, Kugiyama K, Ohgushi M, Fujimoto K, Yasue H (1994) Lysophosphatidylcholine in oxidized low-density lipoprotein increases endothelial susceptibility to polymorphonuclear leukocyte-induced endothelial dysfunction in porcine coronary arteries: role of protein kinase C. Circ Res 74:565–575PubMed Sugiyama S, Kugiyama K, Ohgushi M, Fujimoto K, Yasue H (1994) Lysophosphatidylcholine in oxidized low-density lipoprotein increases endothelial susceptibility to polymorphonuclear leukocyte-induced endothelial dysfunction in porcine coronary arteries: role of protein kinase C. Circ Res 74:565–575PubMed
8.
Zurück zum Zitat Keegan A, Walbank H, Cotter MA, Cameron NE (1995) Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta. Diabetologia 38:1475–1478PubMed Keegan A, Walbank H, Cotter MA, Cameron NE (1995) Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta. Diabetologia 38:1475–1478PubMed
9.
Zurück zum Zitat Palmer AM, Thomas CR, Gopaul N et al. (1998) Dietary antioxidant supplementation reduces lipid peroxidation but impairs vascular function in small mesenteric arteries of the streptozotocin-diabetic rat. Diabetologia 41:148–156CrossRefPubMed Palmer AM, Thomas CR, Gopaul N et al. (1998) Dietary antioxidant supplementation reduces lipid peroxidation but impairs vascular function in small mesenteric arteries of the streptozotocin-diabetic rat. Diabetologia 41:148–156CrossRefPubMed
10.
Zurück zum Zitat Skyrme-Jones RAP, O’Brien RC, Berry KL, Meredith IT (2000) Vitamin E supplementation improves endothelial function in type 1 diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol 36:94–102CrossRefPubMed Skyrme-Jones RAP, O’Brien RC, Berry KL, Meredith IT (2000) Vitamin E supplementation improves endothelial function in type 1 diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol 36:94–102CrossRefPubMed
11.
Zurück zum Zitat Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ (1996) Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347:781–786PubMed Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ (1996) Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347:781–786PubMed
12.
Zurück zum Zitat Yusuf S for the Heart Outcomes Prevention Evaluation Study Investigators (2000) Vitamin E supplementation and cardiovascular events in high risk patients. New Engl J Med 342:154–160CrossRefPubMed Yusuf S for the Heart Outcomes Prevention Evaluation Study Investigators (2000) Vitamin E supplementation and cardiovascular events in high risk patients. New Engl J Med 342:154–160CrossRefPubMed
13.
Zurück zum Zitat Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:23–33CrossRefPubMed Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:23–33CrossRefPubMed
14.
Zurück zum Zitat Wigg SJ, Tare M, Tonta MA, O’Brien RC, Meredith IT, Parkington HC (2001) Comparison of effects of diabetes mellitus on an EDHF-dependent and an EDHF-independent artery. Am J Physiol 281:H232–H240 Wigg SJ, Tare M, Tonta MA, O’Brien RC, Meredith IT, Parkington HC (2001) Comparison of effects of diabetes mellitus on an EDHF-dependent and an EDHF-independent artery. Am J Physiol 281:H232–H240
15.
Zurück zum Zitat Soulis T, Cooper ME, Sastra S et al. (1997) Relative contributions of advanced glycation and nitric oxide synthase inhibition to aminoguanidine-mediated renoprotection in diabetic rats. Diabetologia 40:1141–1151 Soulis T, Cooper ME, Sastra S et al. (1997) Relative contributions of advanced glycation and nitric oxide synthase inhibition to aminoguanidine-mediated renoprotection in diabetic rats. Diabetologia 40:1141–1151
16.
Zurück zum Zitat Van der Pijl JW, Daha MR, van den Born J et al. (1998) Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane. Diabetologia 41:791–798CrossRefPubMed Van der Pijl JW, Daha MR, van den Born J et al. (1998) Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane. Diabetologia 41:791–798CrossRefPubMed
17.
Zurück zum Zitat Candido R, Forbes JM, Thomas MC et al. (2003) A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. Circ Res 92:785–792 Candido R, Forbes JM, Thomas MC et al. (2003) A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. Circ Res 92:785–792
18.
Zurück zum Zitat Stegemann H, Stalder K (1967) Determination of hydroxyproline. Clin Chim Acta 18:267–273PubMed Stegemann H, Stalder K (1967) Determination of hydroxyproline. Clin Chim Acta 18:267–273PubMed
19.
Zurück zum Zitat Wrobel K, Wrobel K, Garay-Sevilla ME, Nava LE, Malacara JM (1997) Novel analytical approach to monitoring advanced glycosylation end products in human serum with on-line spectrophotometric and spectrofluorometric detection in a flow system. Clin Chem 43:1563–1569PubMed Wrobel K, Wrobel K, Garay-Sevilla ME, Nava LE, Malacara JM (1997) Novel analytical approach to monitoring advanced glycosylation end products in human serum with on-line spectrophotometric and spectrofluorometric detection in a flow system. Clin Chem 43:1563–1569PubMed
20.
Zurück zum Zitat Ohara Y, Peterson TE, Zheng B, Kuo JF, Harrison DG (1994) Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation. Arterioscler Thromb 14:1007–1013PubMed Ohara Y, Peterson TE, Zheng B, Kuo JF, Harrison DG (1994) Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation. Arterioscler Thromb 14:1007–1013PubMed
21.
Zurück zum Zitat Cuesta Sanz D, Castro Santa-Cruz M (1986) Simultaneous measurement of retinol and alpha-tocopherol in human serum by high-performance liquid chromotography with ultraviolet detection. J Chromatogr 380:140–144PubMed Cuesta Sanz D, Castro Santa-Cruz M (1986) Simultaneous measurement of retinol and alpha-tocopherol in human serum by high-performance liquid chromotography with ultraviolet detection. J Chromatogr 380:140–144PubMed
22.
Zurück zum Zitat Cotter MA, Love A, Watt MJ, Cameron NE, Dines KC (1995) Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats. Diabetologia 38:1285–1294CrossRefPubMed Cotter MA, Love A, Watt MJ, Cameron NE, Dines KC (1995) Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats. Diabetologia 38:1285–1294CrossRefPubMed
23.
Zurück zum Zitat Keaney JF, Gaziano JM, Xu A et al. (1994) Low-dose α-tocopherol improves and high-dose α-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest 93:844–851PubMed Keaney JF, Gaziano JM, Xu A et al. (1994) Low-dose α-tocopherol improves and high-dose α-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest 93:844–851PubMed
24.
Zurück zum Zitat Faruqi R, de la Motta C, DiCorleto P (1994) Alpha tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells. J Clin Invest 94:592–600PubMed Faruqi R, de la Motta C, DiCorleto P (1994) Alpha tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells. J Clin Invest 94:592–600PubMed
25.
Zurück zum Zitat Boscoboinik D, Szewczyk A, Azzi A (1991) Alpha-tocopherol (vitamin E) regulates vascular smooth muscle cell proliferation and protein kinase C activity. Arch Biochem Biophys 286:264–269PubMed Boscoboinik D, Szewczyk A, Azzi A (1991) Alpha-tocopherol (vitamin E) regulates vascular smooth muscle cell proliferation and protein kinase C activity. Arch Biochem Biophys 286:264–269PubMed
26.
Zurück zum Zitat Hennig B, Enoch C, Chow CK (1987) Protection by vitamin E against endothelial cell injury by linoleic acid hydroperoxides. Nutr Res 7:1253–1260 Hennig B, Enoch C, Chow CK (1987) Protection by vitamin E against endothelial cell injury by linoleic acid hydroperoxides. Nutr Res 7:1253–1260
27.
Zurück zum Zitat Chen X, Touyz RM, Park JB, Schiffrin EL (2001) Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR. Hypertension 38:606–611PubMed Chen X, Touyz RM, Park JB, Schiffrin EL (2001) Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR. Hypertension 38:606–611PubMed
28.
Zurück zum Zitat Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA (2002) Inhibition of protein kinase Cβ prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res 90:107–111CrossRefPubMed Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA (2002) Inhibition of protein kinase Cβ prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res 90:107–111CrossRefPubMed
29.
Zurück zum Zitat Ohara Y, Sayegh HS, Yamin JJ, Harrison DG (1995) Regulation of endothelial constitutive nitric oxide synthase by protein kinase C. Hypertension 25:415–420PubMed Ohara Y, Sayegh HS, Yamin JJ, Harrison DG (1995) Regulation of endothelial constitutive nitric oxide synthase by protein kinase C. Hypertension 25:415–420PubMed
30.
Zurück zum Zitat Muniyappa R, Srinivas PR, Ram JL, Walsh MF, Sowers JR (1998) Calcium and protein kinase C mediate high-glucose-induced inhibition of inducible nitric oxide synthase in vascular smooth muscle cells. Hypertension 31:289–295PubMed Muniyappa R, Srinivas PR, Ram JL, Walsh MF, Sowers JR (1998) Calcium and protein kinase C mediate high-glucose-induced inhibition of inducible nitric oxide synthase in vascular smooth muscle cells. Hypertension 31:289–295PubMed
31.
Zurück zum Zitat Ganz MB, Seftel A (2000) Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol 278:E146–E152 Ganz MB, Seftel A (2000) Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol 278:E146–E152
32.
Zurück zum Zitat Azzi A, Breyer I, Feher M et al. (2000) Specific cellular responses to α-tocopherol. J Nutr 130:1649–1652PubMed Azzi A, Breyer I, Feher M et al. (2000) Specific cellular responses to α-tocopherol. J Nutr 130:1649–1652PubMed
33.
Zurück zum Zitat Sandow SL, Tare M, Coleman HA, Hill CE, Parkington HC (2002) Involvement of myoendothelial gap junctions in the actions of endothelium-derived hyperpolarizing factor. Circ Res 90:1108–1113CrossRefPubMed Sandow SL, Tare M, Coleman HA, Hill CE, Parkington HC (2002) Involvement of myoendothelial gap junctions in the actions of endothelium-derived hyperpolarizing factor. Circ Res 90:1108–1113CrossRefPubMed
34.
Zurück zum Zitat Berry KL, Skyrme-Jones RAP, Cameron JD, O’Brien RC, Meredith IT (1999) Systemic arterial compliance is reduced in young patients with IDDM. Am J Physiol 276:H1839–H1845PubMed Berry KL, Skyrme-Jones RAP, Cameron JD, O’Brien RC, Meredith IT (1999) Systemic arterial compliance is reduced in young patients with IDDM. Am J Physiol 276:H1839–H1845PubMed
35.
Zurück zum Zitat Jeremy JY, Thompson CS, Mikhailidis DP (1992) Differential changes of prostanoid synthesis by the gastrointestinal tract, mesenteric vasculature and hepatic portal vein of diabetic rats: comparison between pair and ad libitum feeding. In Vivo 6:635–639PubMed Jeremy JY, Thompson CS, Mikhailidis DP (1992) Differential changes of prostanoid synthesis by the gastrointestinal tract, mesenteric vasculature and hepatic portal vein of diabetic rats: comparison between pair and ad libitum feeding. In Vivo 6:635–639PubMed
36.
Zurück zum Zitat Huijberts MSP, Wolffenbuttel BHR, Struijker Boudier HAJ et al. (1993) Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats. J Clin Invest 92:1407–1411PubMed Huijberts MSP, Wolffenbuttel BHR, Struijker Boudier HAJ et al. (1993) Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats. J Clin Invest 92:1407–1411PubMed
37.
Zurück zum Zitat Chowienczyk PJ, Brett SE, Gopaul NK et al. (2000) Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with type II diabetes. Diabetologia 43:974–977CrossRefPubMed Chowienczyk PJ, Brett SE, Gopaul NK et al. (2000) Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with type II diabetes. Diabetologia 43:974–977CrossRefPubMed
38.
Zurück zum Zitat Gazis A, White DJ, Page SR, Cockcroft JR (1999) Effect of oral vitamin E (α-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus. Diabetic Med 16:304–311CrossRefPubMed Gazis A, White DJ, Page SR, Cockcroft JR (1999) Effect of oral vitamin E (α-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus. Diabetic Med 16:304–311CrossRefPubMed
Metadaten
Titel
Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats
verfasst von
S. J. Wigg
M. Tare
J. Forbes
M. E. Cooper
M. C. Thomas
H. A. Coleman
H. C. Parkington
R. C. O’Brien
Publikationsdatum
01.06.2004
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 6/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1411-x

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