Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat.
Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat.
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DOI：
10.1016/0024-3205(95)02360-7
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发表时间：
1996-01
期刊：
影响因子：
6.1
通讯作者：
G. Pieper;G. Moore-Hilton;A. Roza
中科院分区：
文献类型：
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作者：
G. Pieper;G. Moore-Hilton;A. Roza
已知内皮功能障碍发生在化学诱导的糖尿病动物模型中。BB糖尿病大鼠是一种遗传性糖尿病易感模型，更类似于I型糖尿病。在这项研究中，我们研究了超氧阴离子自由基和环氧合酶活性在自发性糖尿病BB大鼠主动脉内皮功能障碍中的作用。血管内皮功能进行了研究，在体外主动脉环从8周糖尿病大鼠和年龄匹配的非糖尿病的同窝仔。糖尿病对去甲肾上腺素的反应性没有改变。糖尿病环对乙酰胆碱（但不是硝酸甘油）的舒张功能受损。在对照组和糖尿病组中，100 μM L-硝基精氨酸可消除对乙酰胆碱的舒张作用，但等摩尔浓度的氨基胍（一种诱导型一氧化氮合酶抑制剂）对舒张作用无影响。与10 μM吲哚美辛一起孵育不会改变对照或糖尿病环对乙酰胆碱的舒张。与此相反，20 U/ml的超氧化物歧化酶增加舒张糖尿病环乙酰胆碱，但对对照环乙酰胆碱舒张没有影响。因此，一氧化氮介导的，内皮依赖性舒张基因糖尿病BB大鼠的主动脉环减少。此外，超氧阴离子自由基而不是环氧合酶产物在该遗传性糖尿病模型中的内皮功能障碍中起重要作用。
Endothelial dysfunction is known to occur in chemically-induced animal models of diabetes. The BB diabetic rat is a genetic diabetes-prone model which more closely resembles Type I diabetes mellitus. In this study, we examined the role of Superoxide anion radical and cyclooxygenase activity on endothelial dysfunction in aorta of the spontaneous diabetic BB rat. Vascular endothelial function was studied in vitro in aortic rings from 8-wk diabetic rats and agematched nondiabetic littermates. There was no alteration in reactivity to norepinephrine as a result of diabetes. Relaxation to acetylcholine (but not nitroglycerin) was impaired in diabetic rings. Relaxation to acetylcholine was abolished by 100 μM L-nitroarginine but unaltered by an equimolar concentration of aminoguanidine (an inducible nitric oxide synthase inhibitor) in both control and diabetic rings. Incubation with 10 μM indomethacin did not alter relaxation to acetylcholine in either control or diabetic rings. In contrast, addition of 20 U/ml Superoxide dismutase enhanced relaxation to acetylcholine in diabetic rings but had no effect on relaxation to acetylcholine in control rings. Thus, nitric oxide-mediated, endothelium-dependent relaxation is diminished in aortic rings of the genetic diabetic BB rat. Furthermore, Superoxide anion radicals but not cyclooxygenase products play an important role in endothelial dysfunction in this genetic diabetic model.