Effects of Superoxide Dismutase on the Acetylcholine-induced Relaxation Response in Cholesterol-fed and Streptozotocin-induced Diabetic Mice.

High concentration of acetylcholine (ACh) caused a rapid and long lasting relaxation response in age-matched controls, whereas this response was significantly weaker in streptozotocin (STZ)-diabetic and cholesterol fed mice. The levels of basal and ACh-stimulated cyclic GMP in the aorta was also significantly smaller in STZ-diabetic and cholesterol-fed mice. The attenuated relaxation responses to ACh in both STZ-diabetic and cholesterol-fed mice were ameliorated by the chronic administration of cholestyramine. A prior incubation of aortic strips with superoxide dismutase (SOD, 60 U/ml) improved the recovery phase of the relaxation of diabetic aorta after single administration of ACh, whereas SOD had no effects on ACh-induced relaxation of aortic strips from cholesterol fed mice. These results suggest that superoxide anion may be responsible for an impairment of endothelium-dependent relaxation of aorta from STZ induced diabetic mice. It is further suggested that impairment of endothelium-dependent relaxation in STZ-diabetic and cholesterol fed mice may be caused by different mechanisms.