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.
Kamata
K
K
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan. kamata@hoshi.ac.jp
Nakajima
M
M
Sugiura
M
M
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol; D002792:Cholestyramine Resin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D011863:Radioimmunoassay; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D001786:Blood Glucose; D002792:Cholestyramine Resin; D009569:Nitric Oxide; D013311:Streptozocin; D002784:Cholesterol; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D000109:Acetylcholine