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

Diabetologia. 2004 Jun;47(6):1038-46. doi: 10.1007/s00125-004-1411-x. Epub 2004 Jun 8.

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)-beta(2) 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-beta(2) 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-beta(2) isoform by vitamin E.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Australia
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dietary Supplements
  • Dilatation, Pathologic / complications
  • Dilatation, Pathologic / drug therapy*
  • Dilatation, Pathologic / physiopathology
  • Drug Administration Schedule
  • Elasticity / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Femoral Artery / drug effects
  • Femoral Artery / metabolism*
  • Femoral Artery / pathology
  • Glycated Hemoglobin / metabolism
  • Glycation End Products, Advanced / chemistry
  • Glycation End Products, Advanced / metabolism
  • Indomethacin / pharmacology
  • Isoprostanes / metabolism
  • Lipid Metabolism
  • Lipids / classification
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / enzymology*
  • Mesenteric Arteries / pathology
  • Muscle, Smooth, Vascular / physiology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / chemistry
  • Protein Kinase C / physiology
  • Protein Kinase C beta
  • Rats
  • Rats, Wistar
  • Up-Regulation
  • Vasodilation / physiology
  • Vitamin E / administration & dosage*
  • Vitamin E / blood
  • Vitamin E / therapeutic use*

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Isoprostanes
  • Lipids
  • Vitamin E
  • Protein Kinase C
  • Protein Kinase C beta
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester
  • Indomethacin