Long-term treatment in vivo with NOX-101, a scavenger of nitric oxide, prevents diabetes-induced endothelial dysfunction.
Long-term treatment in vivo with NOX-101, a scavenger of nitric oxide, prevents diabetes-induced endothelial dysfunction.
复制标题
使用一氧化氮清除剂 NOX-101 进行体内长期治疗可预防糖尿病引起的内皮功能障碍。
DOI：
10.1007/s001250051055
复制
发表时间：
1998
期刊：
影响因子：
8.2
通讯作者：
Siebeneich,W
中科院分区：
文献类型：
--
作者：
Pieper,GM;Dembny,K;Siebeneich,W
大量证据表明糖尿病导致内皮功能障碍，表明糖尿病内皮细胞产生的一氧化氮减少。目前尚不清楚是什么因素导致了这种缺陷的发展。在这项研究中，我们测试了用NOX-101（一种水溶性一氧化氮清除剂）在体内长期治疗是否可以预防糖尿病患者的内皮功能障碍。通过静脉注射链脲佐菌素使Sprague-Dawley大鼠患糖尿病。对照或糖尿病动物的亚组在注射链脲佐菌素后48小时开始并且在整个8周的糖尿病期间接受80 mg/kg NOX-101的每日两次皮下注射。每周监测体重和葡萄糖浓度。在8周结束时，糖尿病大鼠的血糖和糖化血红蛋白升高，但血清胰岛素浓度降低。NOX-101治疗并没有改变对照组或糖尿病大鼠的葡萄糖或胰岛素浓度;然而，与未治疗的大鼠相比，总糖化血红蛋白部分减少。在2周糖尿病和年龄匹配的大鼠禁食24小时的亚组中，NOX-101消除了总尿硝酸盐和亚硝酸盐（体内一氧化氮产生的指数）。在离体组织浴中，糖尿病患者主动脉环对内皮依赖性血管扩张剂乙酰胆碱的舒张功能受损，对硝酸甘油的舒张功能不变。用NOX-101治疗对照大鼠并没有改变对乙酰胆碱的最大舒张，但反应曲线略微向右移动。与此相反，在糖尿病大鼠中，NOX-101防止内皮依赖性舒张的损害，但对硝酸甘油引起的舒张没有影响。这些数据表明，糖尿病引起的内皮功能障碍的糖尿病的结果，在某种程度上，从一个矛盾的增加一氧化氮生产过程中的疾病的可能性。这提示了血管并发症的新途径。[Diabetologia（1998）41：1220-1226]
Substantial evidence exists that diabetes results in impaired endothelial dysfunction suggesting diminished nitric oxide production from diabetic endothelium. It is not known what factors contribute to the development of this defect. In this study, we tested whether chronic treatment in vivo with NOX-101, a water-soluble nitric oxide scavenger, prevents endothelial dysfunction in diabetes. Sprague-Dawley rats were made diabetic by an intravenous injection of streptozotocin. A subgroup of control or diabetic animals received twice daily subcutaneous injections of 80 mg/kg NOX-101 beginning at 48 h after streptozotocin was injected and throughout 8 weeks of diabetes. Body weights and glucose concentrations were monitored weekly. At the end of 8 weeks, blood glucose and glycosylated haemoglobin was raised in diabetic rats but serum insulin concentrations were reduced. Treatment with NOX-101 did not alter glucose or insulin concentrations in control or diabetic rats; however, total glycosylated haemoglobin was partially reduced compared with untreated rats. In a subgroup of 2-week diabetic and age-matched rats fasted for 24 h, NOX-101 abolished total urinary nitrate plus nitrite (an index of nitric oxide production in vivo). In isolated tissue baths, relaxation to the endothelium-dependent vasodilator, acetylcholine, was impaired in diabetic aortic rings and relaxation to nitroglycerin was unaltered. Treatment of control rats with NOX-101 did not alter maximum relaxation to acetylcholine but shifted the response curve slightly to the right. In contrast in diabetic rats, NOX-101 prevented the impairment in endothelium-dependent relaxation but had no effect on relaxation induced by nitroglycerin. These data suggest the possibility that diabetes-induced endothelial dysfunction in diabetes results, in part, from a paradoxical increase in nitric oxide production during the course of the disease. This suggests a novel pathway of vascular complications. [Diabetologia (1998) 41: 1220–1226]