General Pharmacology, vol.29, no.4, pp.561-567, 1997 (SCI-Expanded)
1. The present study concerns in vitro isoprenaline (ISO)-induced relaxation of aortic rings of long term streptozotocin (STZ)-diabetic and nondiabetic rats, both with and without dietary vitamin E supplementation. 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 aorta by diabetes. Four months of STZ diabetes results in a significant increase in the ISO-induced relaxations together with endothelial dysfunction in the rat aorta. Diabetes also causes the loss of vascular integrity. 4. Dietary vitamin E supplementation during the last 2 months of diabetes allows normalization of the levels of lipid peroxides. This vitamin also completely reverses the increased sensitivity (pD2 value) of the aorta to ISO, whereas the maximum ISO-induced relaxations are partially restored after the treatment in diabetic rats. 5. The results suggest that ISO-induced relaxation in the aorta partially depends on the intact endothelium and that the endothelium dependent relaxant effect of ISO is mediated by endothelium derived relaxing factor. Results also indicate that abnormal vascular reactivity and structure of the diabetic rat aorta may be related to the increased lipid peroxidation. In conclusion, vitamin E can protect the arterial wall from oxidative stress-induced injury associated with chronic STZ diabetes and allows normalization of the response to ISO and the structure of the aorta in diabetic rats.