Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes

The present study investigated the effects of alpha -lipoic acid treatment (50 mg/kg/day) on the metabolism and vascular condition already damaged by streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism, o xidative stress and antioxidant status were assessed in non-diabetic contro ls, 12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks and then treated with a-lipoic acid for the last 6 weeks) rats. Blo od pressures of rats were measured by tail-cuff method. Vascular reactivity was evaluated in isolated aortic rings. Morphology of aorta was examined b y electron microscopy technique. Alpha-lipoic acid treatment effectively re versed body weight, blood glucose, plasma insulin, cholesterol, triglycerid es and lipid peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood pressure, which was partially improved by alpha -lipoic acid treatment. Although the superoxide dismutase (SOD) activity in aortic homogenates was not changed by diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx) activity significantly increased in untrea ted diabetic rats. Alpha-lipoic acid treatment improved catalase activity i n diabetic aorta. The contractile effect of phenylephrine markedly increase d in diabetic rings, which was completely reversed by alpha -lipoic acid tr eatment. The maximum vasorelaxant response of pre-contracted aortic rings e xposed to cumulatively increased concentrations of acetylcholine was unaffe cted by diabetes or antioxidant treatment. Sodium nitroprusside-induced end othelium-independent relaxations were similar in all experimental groups. V arious alterations caused by STZ-diabetes in aorta structure were partially ameliorated by alpha -lipoic acid treatment. The potency of alpha -lipoic acid on the reversal of hypertension by affecting vascular reactivity and m orphology as well as general metabolism of diabetic rats confirms the impor tance of hyperglycemia-induced oxidative stress in the development of diabe tes-induced vascular complications and suggests a potential therapeutic app roach. (C) 2000, Editrice Kurtis.