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. Antioxidants in Diabetes-Induced Complications (ADIC) Study Group.
In this study, we evaluated the effects of vitamin E on the vascular reactivity and structure of thoracic aorta from streptozotocin (STZ)-diabetic rats. Plasma glucose, cholesterol, and triglyceride concentrations in rats were increased markedly by STZ-diabetes. The thiobarbituric acid (TBA) reactivity level as an index of lipid peroxidation was higher in both plasma and aorta of STZ-diabetic rats compared with controls. The rings of thoracic aorta with or without endothelium were mounted in organ chambers for measurement of isometric tension and were contracted by a single dose (10-5 mol/L) and then cumulative doses of noradrenaline ([NA] 10(-9) to 10(-5) mol/L). Pretreatment with methylene blue (MB) or removal of the endothelium resulted in a similar degree of enhancement in NA-induced contraction of control rings. STZ-diabetes increased the fast and slow components of NA-induced contraction in all experiments. The maximal contractile response of aorta to NA was also augmented by STZ-diabetes, whereas the sensitivity (pD2) remained unaltered. STZ-diabetes resulted in significant increases in the maximum contractile response and sensitivity of aorta to KCl. STZ-diabetic rats showed a significant reduction in the percentage of endothelial response (PER). A group of diabetic rats was treated from the time of diabetes induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned plasma triglycerides toward normal levels. Diabetes-induced abnormal contractility and endothelial dysfunction were significantly but not completely prevented by vitamin E treatment. The endothelium-independent relaxation response to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E treatment. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E treatment can protect the morphological integrity of aorta against STZ-diabetes. The results suggest the following: (1) The increased triglycerides/lipid peroxides may be an important reason for morphological or functional disruption of endothelium and enhanced activation of contractile mechanisms of vascular smooth muscle in STZ-diabetic rats. Both contribute to an increased responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E treatment of STZ-diabetic rats can prevent the development of abnormal contractility and structure and endothelial dysfunction in aorta. (3) The triglyceride- and/or lipid peroxidation-lowering effect of vitamin E may be crucial for the protective effect of this vitamin on the vasculature.
Karasu
C
C
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Turkey.
Ozansoy
G
G
Bozkurt
O
O
Erdoğan
D
D
Omeroğlu
S
S
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D014280:Triglycerides / Q000097:blood*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D014280:Triglycerides; D014665:Vasodilator Agents; D014810:Vitamin E; D009599:Nitroprusside; D002784:Cholesterol