Effect of chronic insulin treatment on NO production and endothelium-dependent relaxation in aortae from established STZ-induced diabetic rats

The hypothesis that the impaired endothelial function seen in streptozotoci n (STZ)-induced diabetic rats may result From an increased nitric oxide (NO ) metabolism was tested. Acetylcholine (ACh) increased the nitrite NO2- and nitrate (NO3-) levels in the perfusates from both control and diabetic aor tic strips. although the level of NO2- was significantly lower in diabetic rats while the NO3- level was significantly higher. Both effects (decrease in NO2- and increase in NO3-) were ameliorated by chronic administration of insulin to diabetic rats but NOx (NO2 plus NO3-) was increased. The expres sion of endothelial nitric oxide synthase (eNOS) was significantly increase d by chronic administration of insulin to diabetic rats. A decrease in NO2- and an increase in NO3- occurred following treatment of control aortae wit h hypoxanthine/xanthine oxidase. incubating diabetic aot tic strips with su peroxide dismutase (SOD) normalized the production of both NO2- and NO3-. B oth the basal and the ACh-stimulated production of O-2(-) were significantl y higher in diabetic rats than in controls. These results demonstrate that the ACh-induced relaxation of aortic strips was significantly impaired in d iabetic rats and that this impairment may be due to an abnormal oxidative m etabolism of NO, rather than to a decrease in NOS mRNA and NO production. ( C) 2001 Elsevier Science Ireland Ltd. All rights reserved.