Dietary antioxidant supplementation reduces lipid peroxidation but impairs vascular function in small mesenteric arteries of the streptozotocin-diabetic rat.
Impaired endothelium-dependent relaxation could underlie many of the vascular complications associated with insulin-dependent diabetes mellitus, and may be mediated by increased oxidative stress. The effect of antioxidants on vascular endothelial function and oxidative stress of streptozotocin-diabetic rats was assessed by dietary supplementation with vitamins E and C. Diabetic (i.v. streptozotocin, 45 mg/kg) male Sprague-Dawley rats were fed one of six supplemented diets containing 75.9, 250, or 500 mg vitamin E/kg chow, 250 mg vitamin C/kg H2O, 250 mg vitamin E/kg chow plus 250 mg vitamin C/kg H2O, or chow deficient in vitamin E, and then compared to standard-fed control rats. After 4 weeks, small mesenteric arteries were dissected and mounted on a small vessel myograph, concentration response curves were then constructed to noradrenaline, acetylcholine and sodium nitroprusside. Acetylcholine-mediated relaxation was impaired in arteries from diabetic rats (pEC50 6.701+/-SEM 0.120, n = 8) compared to controls (7.386+/-0.078, n = 6; p < 0.05). The 500 mg/kg vitamin E diet further impaired maximum relaxation to acetylcholine (58.2+/-10.5 vitamin E, n = 7 vs 84.4+/-5.3 % standard, p < 0.05), and the combined vitamin E plus C diet impaired maximum relaxation to sodium nitroprusside (48.5+/-4.1 in vitamin E + C, n = 8 vs 75.6+/-3.9 % standard; p < 0.01). However, plasma 8-epi-prostaglandin (PG)F2alpha (measured as an estimate of oxidative stress) was dose-dependently decreased in rats on vitamin E supplemented diets. Dietary antioxidant supplementation did not reverse impaired endothelial function in this model of uncontrolled diabetes despite a concomitant decrease in oxidative stress.
Palmer
A M
AM
United Medical and Dental Schools, St Thomas' Hospital, London, UK.
Thomas
C R
CR
Gopaul
N
N
Dhir
S
S
Anggård
E E
EE
Poston
L
L
Tribe
R M
RM
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D028441:F2-Isoprostanes; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D009126:Muscle Relaxation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity
D000975:Antioxidants; D028441:F2-Isoprostanes; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D001205:Ascorbic Acid