Relationship among cholesterol, superoxide anion and endothelium-dependentrelaxation in diabetic rats

The purpose of the present study was to investigate the time course of chan ges in plasma low-density lipoprotein (LDL) cholesterol, tissue lipid perox idation, the expression of hepatic LDL-receptor mRNA and aortic superoxide dismutase, and the relaxation response to acetylcholine in streptozotocin-i nduced diabetic rats. Plasma cholesterol and LDL levels were significantly increased in both 4- and 10-week diabetic rats. The tissue malonic dialdehy de content in aortas was increased in 10-week compared to 1- or 4-week diab etic rats. The expression of mRNA for LDL receptor mRNA in the liver showed a decrease in both 4- and 10-week diabetic rats. Hepatic LDL-receptor bind ing activity decreased significantly in 10-week diabetic rats, and decrease d binding activity in diabetic rats was improved by the chronic administrat ion of cholestyramine. The relaxation responses to acetylcholine in helical strips of the aorta precontracted with noradrenaline were significantly de creased in 10-week, but not in 1- or 4-week streptozotocin-induced diabetic rats. The decreased relaxation response to acetylcholine was improved by c hronic cholestyramine. Both the expression of Mn-superoxide dismutase mRNA and the activity of superoxide dismutase in the aorta were decreased in 10- week, but not in 4-week diabetic rats. From time-course studies, our data s uggest that not only increased LDL cholesterol but also decreased activity of superoxide dismutase are responsible for the decreased relaxation respon se induced by acetylcholine. (C) 1999 Elsevier Science B.V. All rights rese rved.