Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.
Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
G M
GM
Pieper
W
W
Siebeneich
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology* / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D016166:Free Radical Scavengers; D000111:Acetylcysteine; D009638:Norepinephrine