title: 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.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Physiology, Monash University, 3800 Melbourne, Victoria, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wigg
authors.forename: M
authors.initials: M
authors.lastname: Tare
authors.forename: J
authors.initials: J
authors.lastname: Forbes
authors.forename: M E
authors.initials: ME
authors.lastname: Cooper
authors.forename: M C
authors.initials: MC
authors.lastname: Thomas
authors.forename: H A
authors.initials: HA
authors.lastname: Coleman
authors.forename: H C
authors.initials: HC
authors.lastname: Parkington
authors.forename: R C
authors.initials: RC
authors.lastname: O'Brien
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001315:Australia; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D019587:Dietary Supplements; D004108:Dilatation, Pathologic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004548:Elasticity / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D028421:Isoprostanes / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000145:classification; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D064546:Protein Kinase C beta; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D014664:Vasodilation / Q000502:physiology; D014810:Vitamin E / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000109:Acetylcholine; D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007213:Indomethacin; D028421:Isoprostanes; D008055:Lipids; D019331:NG-Nitroarginine Methyl Ester; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D014810:Vitamin E