CHRONIC TREATMENT IN-VIVO WITH DIMETHYLTHIOUREA, A HYDROXYL RADICAL SCAVENGER, PREVENTS DIABETES-INDUCED ENDOTHELIAL DYSFUNCTION

Oxidative stress is believed to play a role in diabetes-induced vascul ar complications. In this study, we tested whether chronic treatment w ith a known hydroxyl radical scavenger, dimethylthiourea (DMTU), could prevent endothelial dysfunction in diabetes. Lewis strain rats were m ade diabetic by an intravenous injection of streptozotocin. A subgroup of diabetic animals received daily intraperitoneal injections of 50 m g/kg DMTU beginning at 72 h after streptozotocin and throughout 8 week s of diabetes. Diabetes caused an increase in aortic catalase activity (an index of compensatory in vivo oxidative stress) that was not prev ented by long-term DMTU treatment. Long-term treatment of diabetic ani mals with DMTU did not alter serum insulin levels, blood glucose conce ntrations, or total glycosylated hemoglobin. Descending thoracic aorta s were isolated, sectioned into rings and suspended in isolated tissue baths, and contracted with a submaximal concentration of norepinephri ne. Relaxation to the endothelium-dependent vasodilator, acetylcholine , was impaired in diabetic aortas, whereas relaxation to A23187 and ni troglycerin was unaltered. DMTU treatment prevented the diabetes-induc ed impairment in endothelium-dependent relaxation to acetylcholine but had no effect on relaxations induced by either A23187 or nitroglyceri n. These data suggest that chronic exposure to increased levels of hyd roxyl radicals in vivo likely play a significant role in the origin of diabetes-associated endothelial dysfunction.