DIABETES-INDUCED ENDOTHELIAL DYSFUNCTION IS PREVENTED BY LONG-TERM TREATMENT WITH THE MODIFIED IRON CHELATOR, HYDROXYETHYL STARCH CONJUGATED-DEFEROXAMINE

Oxygen radicals are believed to play a role in vascular complications of diabetes mellitus. In this study, we evaluated whether long-term tr eatment with an iron chelator and inhibitor of metal-catalyzed hydroxy l radicals (. OH) could prevent diabetes-induced defects in endotheliu m-dependent relaxation. Diabetes was induced in Sprague-Dawley;ley rat s by injection of streptozotocin. At 48 h after streptozotocin, a subg roup of diabetic rats received daily injections of 50 mg/kg hydroxyeth yl starch conjugated-deferoxamine (HES-DFO) for a total of 8 weeks. Lo ng-term treatment with HES-DFO did not modify serum insulin or blood g lucose taken at the end of the study; however, a modest reduction in g lycosylated hemoglobin was present. In precontracted aortic rings susp ended in tissue baths, endothelium-dependent relaxation to acetylcholi ne was impaired in diabetic rings compared with control rings in the p resence or absence of indomethacin. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term treatment with HES-DFO had Ilo effect on relaxation to nitroglycerin but completely prevented the impaired relaxation to acetylcholine in diabetic rings in either the presence or absence of indomethacin. ?These data suggest that iron-cat alyzed . OH formation contributes to the development of diabetes-assoc iated endothelial dysfunction.