Location of Repository

Hydrogen Peroxide-Induced Inhibition of Vasomotor Activity: Evaluation of Single and Combined Treatments With Vitamin A and Insulin in Streptozotocin-Diabetic Rats

By Fulya Zobali, Tanju Besler, Nuray Ari and Çimen Karasu


A positive correlation has been established between increased oxidative stress and cardiovascular diseases in diabetes mellitus. We evaluated the effects of single or combined treatments with vitamin A (retinol acetate, 30 mg/kg/day, for 12-weeks) and insulin (8-10 IU/rat/day for the final 6-week) on vasomotor activity, oxidative stress and retinol metabolism in 12-week streptozotocin diabetic rats. The vasomotor activity was determined by measuring in vitro responsiveness of aorta rings to phenylephrine (PE) and acetylcholine (ACh) in the absence or in the presence of hydrogen peroxide (H2O2). Preincubation with H2O2 (10 μM) produced a significant decrease in PE (1 mM)-induced contraction in untreated-diabetic but not in control rats. Single treatment with insulin counteracted this effect of H2O2 and also reversed the increased contractile response of diabetic aorta to PE, while vitamin A was found to be ineffective. H2O2 (10 μM) also inhibited ACh (1 mM)-stimulated endothelium- dependent relaxation two fold more in diabetic than in control aorta. In the prevention of H2O2-induced inhibition of vascular relaxation to ACh, vitamin A alone was markedly effective while insulin alone was not. The combination of vitamin A plus insulin removed the inhibitory action of H2O2 in diabetic aorta. Diabetic animals displayed an increased level of aorta thiobarbituric acid reactive substance (TBARS) in association with decreased levels of plasma retinol and retinol-binding protein (RBP). Single treatment with insulin, in spite of allowing recovery of normal growth rate and improved glucose and retinol metabolism in diabetic rats, was unable to control TBARS production to the same extent as vitamin A alone. Our findings suggest that the maintenance of ACh-stimulated endothelium-dependent vasorelaxant tone in normal physiological levels depends largely on the prevention and/or inhibition of peroxidative stress, which is achieved by combined treatment with vitamin A plus insulin. The use of vitamin A together with insulin provides a better metabolic control and more benefits than use of insulin alone in the reduction of diabetes-induced vascular complications

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:2478572
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (1976). Activation of soluble guanylate cyclase from rat lung by incubation or by hydrogen peroxide,
    2. (1998). Acute Probucol treatment partially restores vasomotor activity and abnormal lipid metabolism whereas morphological changes are not affected in aorta from long-term STZ-diabetic rats, Exp Clin Endocrinol Diabetes,
    3. (2000). Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes
    4. (1997). Antioxidant and triglyceride lowering effects of vitamin E associated with the prevention of abnormalities in the reactivity and morphology of aorta from streptozotocin-diabetic rats,
    5. (1997). Changes in isoprenaline-induced endothelium-dependent and –independent relaxations of aorta in long-term STZ-diabetic rats: Reversal effect of dietary vitamin E,
    6. (1995). Contribution of vitamin A to the oxidation resistance of human low density lipoproteins,
    7. (1991). Cytosolic free Ca2+ and proteolysis in lethal oxidative injury in endothelial cells,
    8. (1996). Decrease in Ca2+ sensitivity as a mechanism of hydrogen peroxide-induced relaxation of rabbit aorta,
    9. (1985). Determination of vitamins A and E in serum and plasma using a simplified clarification method and high-performance liquid chromatography.
    10. (1993). Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits Proc Natl Acad Sci
    11. (1995). Effect of vitamins A and E on ischemia-reperfusion damage in rabbit heart,
    12. (1995). Effects of anti-oxidant treatment on sciatic nerve dysfunction in streptozotocin-diabetic rats; comparison with essential fatty acids,
    13. (1999). Effects of diabetes and treatment with the antioxidant alpha-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats,
    14. (1995). Effects of dietary fats, alpha-tocopherol and beta-carotene supplementation on aortic ring segment responses in the rat,
    15. (1995). Effects of H2O2 on membrane potential and Ca2+ i of cultured rat arterial smooth muscle cells,
    16. (2000). Effects of hydrogen peroxide on pig coronery artery endothelium,
    17. (1995). Elevated lipid peroxidation and vitamin E-quinone levels in heart ventricles of streptozotocin treated diabetic rats,
    18. (1992). Glucose and diabetic vascular disease,
    19. (1995). High retinol/retinol-binding protein ratio in noninsulin-dependent diabetes mellitus,
    20. (2000). Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice,
    21. (1999). Hydrogen peroxide-induced endothelium-dependent relaxation of rat aorta involvement of Ca2+ and other cellular metabolites,
    22. (1997). Hydrogen peroxideinduced impairment of reactivity in rat isolated aorta: potentiation by 3-amino-1,2,4-triazole,
    23. (1993). Immunonephelometry and radial immunodiffusion compared for measuring serum retinol-binding protein,
    24. (1999). Increased activity of H2O2 in aorta isolated from chronically streptozotocin-diabetic rats: effects of antioxidant enzymes and enzymes inhibitors,
    25. (1993). Increased risk of cardiovascular disease at suboptimal plasma concentration of essencial antioxidants: an epidemiological update with special attention to carotene and vitamin C,
    26. (1988). Insulin induced reversibility of altered responsiveness in femoral arterial bed of diabetic dogs,
    27. (1994). Insulin’s effect on protein kinase C and diacylglycerol induced by diabetes and glucose in vascular tissues,
    28. (1993). Involvement of nitric oxide in the endothelium-dependent relaxation induced by hydrogen peroxide in the rabbit aorta,
    29. (1976). Microzommal enzyme inducers and hypervitaminossis A in rats,
    30. (1996). Oxidative stress and diabetic vascular complications,
    31. (2000). Oxidative stress augments secretion of endothelium-derived relaxing peptides, C-type natriuretic peptide and adrenomedulin,
    32. (1993). Plasma retinol and alpha-tocopherol concentrations in insulin-dependent diabetes mellitus: their relationship to microvascular complications,
    33. (1993). Possible superoxide radical-induced alteration of vascular reactivity in aortas from streptozotocin-treated rats,
    34. (1993). Prophylactic effect of vitamin A, neutralizing the development of experimental insulin-dependent diabetes in animals,
    35. (1989). Protective effects of retinyl palmitate on streptozotocin- and alloxan-induced beta cell toxicity and diabetes in the rat,
    36. (1998). Protein kinase C activation and the development of diabetic complications,
    37. (1996). Streptozotocin-induced diabetes in rats is associated with impaired metabolic availability of vitamin A (retinol),
    38. (1992). Superoxide stimulates IP3-induced Ca2+ release from vascular smooth muscle sarcoplasmic reticulum,
    39. (1985). The effect of insulin treatment on changes in vascular reactivity in chronic, experimental diabetes,
    40. (2000). The metabolic availability of vitamin A is decreased at the onset of diabetes in BB rats,
    41. (1993). The role of endothelial cells on the alterations in vascular reactivity induced by insulin-dependent diabetes mellitus: Effects of insulin treatment,
    42. (2000). Time course of changes in endotheliumdependent and -independent relaxation of chronically diaEFFECT
    43. (1994). Transport and metabolism of vitamin A.
    44. (1997). Vitamin A homeostasis and diabetes mellitus,

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.