Contractile responses in spontaneously diabetic mice. I. Involvement of superoxide anion in enhanced contractile response of aorta to norepinephrine in C57BL/KsJ(db/db) mice.
This study investigated the influence of superoxide anion on the norepinephrine (NE)-induced contractile response in spontaneously diabetic mice. In aortic rings with intact endothelium, NE elicited only a slight increase in tension in nondiabetic mice (db/+M), but a much greater dose-dependent contraction in spontaneously diabetic mice (db/db mice). The NE-induced contractile response was significantly reduced by pretreatment with SOD (180 U/ml) in diabetic mice, but not in control mice. The NE-induced contraction was significantly enhanced by pretreatment with diethyldithiocarbamic acid (DETCA, 10(-3) M), a Cu/Zn SOD inhibitor, in control mice, but not in diabetic mice. The dose-response curve for the acetylcholine-induced relaxation was slightly, but significantly attenuated in diabetic mice. When aortic rings from control mice were incubated with a mixture of hypoxanthine (10(-5) M), xanthine oxidase (0.1 U/ml) and catalase (1000 U/ml) in control mice, they gradually contracted. This contraction was abolished by pretreatment with SOD (180 U/ml) or indomethacin (10(-5) M) or by removal of the endothelium. The enhanced NE-induced dose-dependent contraction seen in diabetic mice was markedly attenuated by indomethacin. These results suggest that in db/db diabetic mice, superoxide anion, perhaps via vasoconstrictor prostanoids, may enhance the contraction induced by NE.
Kanie
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Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Kamata
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000097:blood; D013481:Superoxides / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine; D007213:Indomethacin