Oxygen-derived free radicals mediate endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes
| Autor: | Vanhoutte, PM, Man, RYK, So, KF, Shi, Y |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Superoxide Dismutase - drug effects - metabolism Endothelium-derived contracting factor Hydrogen Peroxide - antagonists & inhibitors - pharmacology Calcimycin - pharmacology Enzyme Activation - drug effects Vasoconstriction - drug effects Reactive Oxygen Species - metabolism Diabetes Mellitus Experimental - chemically induced - metabolism - physiopathology Oxygen-derived free radicals Femoral Artery - drug effects - metabolism - physiopathology Streptozocin Catalase - drug effects - metabolism Rats Sprague-Dawley Organ Culture Techniques Signal Transduction - drug effects Animals Endothelium Vascular - drug effects - metabolism Endothelium-dependent contractions Antioxidants - pharmacology Dose-Response Relationship Drug Rats Disease Models Animal Oxidants - pharmacology Streptozotocin-induced diabetes Oxidative stress Microscopy Confocal - methods Enzyme Inhibitors - pharmacology Oxidation-Reduction |
| Popis: | Background and purpose: The present experiments were designed to study the contribution of oxygen-derived free radicals to endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes. Experimental approach: Rings with and without endothelium were suspended in organ chambers for isometric tension recording. The production of oxygen-derived free radicals in the endothelium was measured with 2′,7′- dichlorodihydrofluorescein diacetate using confocal microscopy. The presence of protein was measured by western blotting. Key results: In the presence of L-NAME, the calcium ionophore A23187 induced larger endothelium-dependent contractions in femoral arteries from diabetic rats. Tiron, catalase, deferoxamine and MnTMPyP, but not superoxide dismutase reduced the response, suggesting that oxygen-derived free radicals are involved in the endothelium-dependent contraction. In the presence of L-NAME, A23187 increased the fluorescence signal in femoral arteries from streptozotocin-treated, but not in those from control rats, confirming that the production of oxygen-derived free radicals contributes to the enhanced endothelium-dependent contractions in diabetes. Exogenous H 2O 2 caused contractions in femoral arterial rings without endothelium which were reduced by deferoxamine, indicating that hydroxyl radicals contract vascular smooth muscle and thus could be an endothelium-derived contracting factor in diabetes. The reduced presence of Mn-SOD and the decreased activity of catalase in femoral arteries from streptozotocin-treated rats demonstrated the presence of a redox abnormality in arteries from rats with diabetes. Conclusions and implications: These findings suggest that the redox abnormality resulting from diabetes increases oxidative stress which facilitates and/or causes endothelium-dependent contractions. © 2007 Nature Publishing Group All rights reserved. link_to_OA_fulltext |
| Databáze: | OpenAIRE |
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