CHANGES IN ISOPRENALINE-INDUCED ENDOTHELIUM-DEPENDENT AND ENDOTHELIUM-INDEPENDENT RELAXATIONS OF AORTA IN LONG-TERM STZ-DIABETIC RATS - REVERSAL EFFECT OF DIETARY VITAMIN-E

1. The present study concerns in vitro isoprenaline (ISO)-induced rela xation of aortic rings of long-term streptozotocin (STZ)-diabetic and nondiabetic rats, both with and without dietary vitamin E supplementat ion. 2. Incubation with propranolol, N-G-nitro L-arginine methyl ester and methylene blue, as well as absence of endothelium, all negatively affect the ISO-induced relaxations. 3. Thiobarbituric acid reactivity levels used as an index of lipid peroxidation are elevated in the aor ta by diabetes. Four months of STZ diabetes results in a significant i ncrease in the ISO induced relaxations together with endothelial dysfu nction in the rat aorta. Diabetes also causes the loss of vascular int egrity. 4. Dietary vitamin E supplementation during the last 2 months of diabetes allows normalization of the levels of lipid peroxides. Thi s vitamin also completely reverses the increased sensitivity (pD(2) va lue) of the aorta to ISO, whereas the maximum ISO induced relaxations are partially restored after the treatment in diabetic rats. 5. The re sults suggest that ISO-induced relaxation in the aorta partially depen ds on the intact endothelium and that the endothelium-dependent relaxa nt effect of ISO is mediated by endothelium-derived relaxing factor. R esults also indicate that abnormal vascular reactivity and structure o f the diabetic rat aorta may be related to the increased lipid peroxid ation. In conclusion, vitamin E can protect the arterial wall from oxi dative stress-induced injury associated with chronic STZ-diabetes and allows normalization of the response to ISO and the structure of the a orta in diabetic rats. (C) 1997 Elsevier Science Inc.