ROLE OF OXYGEN-DERIVED RADICALS FOR VASCULAR DYSFUNCTION IN THE DIABETIC HEART - PREVENTION BY ALPHA-TOCOPHEROL

The evidence that the generation of reactive oxygen intermediates (ROI ) plays an important role for the increased cardiovascular risk in dia betes is summarised. In addition to the well known parameters of oxida tive stress as lipid hydroperoxides and thiobarbituric acid substances (TBARS), recent observations indicate that isoprostanes which can be taken as a more specific parameter of oxidative stress, are generated in higher amounts by diabetic patients. This increased formation of is oprostanes can be inhibited by an instalment of a close metabolic cont rol or the supplementation with tocopherol. The cause for the elevated oxidative stress is not yet fully understood, however the autoxidatio n of glucose, the formation of advanced glycation endproducts and the activation of NADPH-oxidase seem to be relevant processes. Since ROI a re able to quench nitric oxide and to inhibit the synthesis of prostac yclin, the antithrombotic, vasodilating and antiatherosclerotic proper ties of endothelium are impaired in diabetes. Additionally, the balanc e of endothelial mediators released by endothelium is shifted to angio tensin II and endothelin, compounds which enhance the proliferation of smooth muscle cells and may limit the coronary reserve of myocardium. The activation of the transcription factor NF-kappa B by glucose and its autoxidative products is regarded as a key event in the transforma tion of the vasculature in diabetes. Epidemiological observations and very recent clinical studies underlie the impact of ROI for the develo pment of cardiovascular complications in diabetes and suggest that an antioxidative treatment might be helpful to reduce the cardiac risk in diabetes.