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
| Autor: | N, Kanie, K, Kamata |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Blood Glucose
Male Vasodilator Agents Indomethacin Aorta Thoracic In Vitro Techniques Nitroarginine Muscle Smooth Vascular Mice Norepinephrine Superoxides Isometric Contraction Diabetes Mellitus Animals Insulin Vasoconstrictor Agents Enzyme Inhibitors Dose-Response Relationship Drug Superoxide Dismutase Anti-Inflammatory Agents Non-Steroidal Body Weight Acetylcholine Mice Inbred C57BL Muscle Tonus Potassium Nitric Oxide Synthase Muscle Contraction |
| Zdroj: | General pharmacology. 35(6) |
| ISSN: | 0306-3623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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