Diabetic-induced endothelial dysfunction in rat aorta: role of hydroxyl radicals.
Diabetic-induced endothelial dysfunction in rat aorta: role of hydroxyl radicals.
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DOI：
10.1016/s0008-6363(96)00237-4
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发表时间：
1997-04
影响因子：
10.8
通讯作者：
G. Pieper;P. Langenstroer;W. Siebeneich
中科院分区：
文献类型：
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作者：
G. Pieper;P. Langenstroer;W. Siebeneich
目的：以往的研究表明超氧阴离子自由基（·O2−）在糖尿病血管内皮依赖性舒张功能受损中的作用;然而，次级活性氧的作用仍不清楚。在本研究中，我们探讨了各种潜在的活性氧在糖尿病内皮dysfunction.Methods的作用：胸主动脉环8周链脲佐菌素诱导的糖尿病和年龄匹配的对照组大鼠安装在隔离的组织浴。内皮依赖性松弛乙酰胆碱（ACH）和内皮非依赖性松弛硝酸甘油（NTG）进行了评估，在precontracted rings.Results：ACH诱导的舒张受损糖尿病相比，控制环，并没有改善与吲哚美辛或达曲班。对照组和糖尿病组血管环的ACH诱导的舒张反应可被一氧化氮合酶抑制剂l-硝基精氨酸甲酯或l-硝基精氨酸（l-NA）完全阻断。NTG诱导的舒张对tol-NA不敏感，并且不受糖尿病的影响。超氧化物歧化酶（SOD）预处理的活动，不改变收缩张力未能改变糖尿病环的ACH反应。使用过氧化氢酶或甘露醇获得了类似的结果。相反，SOD加过氧化氢酶或金属促进羟基自由基（·OH）形成的抑制剂CIPPAC的组合显著增强了糖尿病患者对ACH的舒张，但在对照组中没有。无论是SOD加过氧化氢酶，也不改变的敏感性或放松NTG在控制环或无内皮细胞。在有内皮的糖尿病血管环中，NAPAC或SOD加过氧化氢酶增加了对NTG的敏感性，但没有最大舒张作用。在无内皮的糖尿病血管环中，两种治疗均未改变血管舒张和对NTG的敏感性。INl-NA处理的糖尿病血管环具有内皮，DETAPAC或SOD加过氧化氢酶均未改变对NTG的敏感性和松弛性。结论：糖尿病内皮细胞产生·O2-和H2 O2增加，导致细胞内·OH产生增加。因此，·OH与糖尿病诱导的内皮功能障碍有关。
Objective:Previous studies suggest a role of superoxide anion radicals (·O2−) in impaired endothelium-dependent relaxation of diabetic blood vessels; however, the role of secondary reactive oxygen species remains unclear. In the present study, we investigated a role of various potential reactive oxygen species in diabetic endothelial dysfunction.Methods:Thoracic aortic rings from 8-week streptozotocin-induced diabetic and age-matched control rats were mounted in isolated tissue baths. Endothelium-dependent relaxation to acetylcholine (ACH) and endothelium-independent relaxation to nitroglycerin (NTG) were assessed in precontracted rings.Results:ACH-induced relaxation was impaired in diabetic compared to control rings and was not improved with either indomethacin or daltroban. ACH-induced relaxation in both control and diabetic rings was completely blocked with the nitric oxide synthase inhibitors,l-nitroarginine methyl ester orl-nitroarginine (l-NA). NTG-induced relaxation was insensitive tol-NA and was unaltered by diabetes. Pretreatment with superoxide dismutase (SOD) at activities which did not alter contractile tone failed to alter responses to ACH in diabetic rings. Similar results were obtained using either catalase or mannitol. In contrast, the combination of SOD plus catalase or DETAPAC, an inhibitor of metal-facilitated hydroxyl radical (·OH) formation, markedly enhanced relaxation to ACH in diabetic but not in control rings. Neither the combination of SOD plus catalase nor DETAPAC altered the sensitivity or relaxation to NTG in control rings with or without endothelium. In diabetic rings with endothelium, both DETAPAC or SOD plus catalase increased sensitivity but not maximum relaxation to NTG. In diabetic rings without endothelium, relaxation and sensitivity to NTG were unaltered by either treatment. Inl-NA-treated diabetic rings with endothelium, sensitivity and relaxation to NTG was unaltered by either DETAPAC or SOD plus catalase.Conclusion:Diabetic endothelium produces increases in both ·O2−and H2O2leading to enhanced intracellular production of ·OH. Thus, ·OH are implicated in diabetes-induced endothelial dysfunction.