Changes in isoprenaline-induced endothelium-dependent and -independent relaxations of aorta in long-term STZ-diabetic rats: reversal effect of dietary vitamin E.
1. The present study concerns in vitro isoprenaline (ISO)-induced relaxation of aortic rings of long-term streptozotocin (STZ)-diabetic and nondiabetic rats, both with and without dietary vitamin E supplementation. 2. Incubation with propranolol, NG-nitro-L-arginine methyl ester and methylene blue, as well as absence of endothelium, all negatively affect the ISO-induced relaxations. 3. Thiobarbituric acid reactivity levels used as an index of lipid peroxidation are elevated in the aorta by diabetes. Four months of STZ-diabetes results in a significant increase in the ISO-induced relaxations together with endothelial dysfunction in the rat aorta. Diabetes also causes the loss of vascular integrity. 4. Dietary vitamin E supplementation during the last 2 months of diabetes allows normalization of the levels of lipid peroxides. This vitamin also completely reverses the increased sensitivity (pD2 value) of the aorta to ISO, whereas the maximum ISO-induced relaxations are partially restored after the treatment in diabetic rats. 5. The results suggest that ISO-induced relaxation in the aorta partially depends on the intact endothelium and that the endothelium-dependent relaxant effect of ISO is mediated by endothelium-derived relaxing factor. Results also indicate that abnormal vascular reactivity and structure of the diabetic rat aorta may be related to the increased lipid peroxidation. In conclusion, vitamin E can protect the arterial wall from oxidative stress-induced injury associated with chronic STZ-diabetes and allows normalization of the response to ISO and the structure of the aorta in diabetic rats.
Karasu
C
C
Department of Pharmacology, Ankara University, Turkey.
Ozansoy
G
G
Bozkurt
O
O
Erdoğan
D
D
Omeroğlu
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D009126:Muscle Relaxation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013311:Streptozocin; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D001786:Blood Glucose; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D009569:Nitric Oxide; D013311:Streptozocin; D011433:Propranolol; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester