ENDOTHELIAL DYSFUNCTION IN MESENTERIC RESISTANCE ARTERIES OF DIABETIC RATS - ROLE OF FREE-RADICALS
ENDOTHELIAL DYSFUNCTION IN MESENTERIC RESISTANCE ARTERIES OF DIABETIC RATS - ROLE OF FREE-RADICALS
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DOI：
10.1152/ajpheart.1994.266.3.h1153
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发表时间：
1994-03-01
影响因子：
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通讯作者：
DAI, FX
中科院分区：
文献类型：
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作者：
DIEDERICH, D;SKOPEC, J;DAI, FX
通过注射链脲佐菌素（55 mg/kg）诱导大鼠糖尿病。在肌电图中比较了对照组和糖尿病大鼠肠系膜阻力动脉（管腔直径210 +/- 20 μ m）的内皮依赖性舒张。乙酰胆碱诱导内皮依赖性舒张，这是由一氧化氮（EDNO）介导。EDNO介导的舒张作用在糖尿病动脉中受损; 6周后，对照组和糖尿病大鼠动脉中产生激活动脉50%舒张（艾德（50））所需的乙酰胆碱浓度分别为5 nM和13.5 nM（P < 0.05）。随着糖尿病病程的延长，血管舒张功能受损加重;在糖尿病16周和24周后，研究的糖尿病动脉中乙酰胆碱的艾德（50）分别增加至63和100 nM。NG-硝基-L-精氨酸使对照组和糖尿病组动脉对乙酰胆碱的敏感性分别降低5.5倍和16倍。NG-硝基-L-精氨酸至少对糖尿病动脉中的乙酰胆碱松弛产生同样多的抑制，表明糖尿病动脉中注意到的松弛受损不是由于EDNO产生减少。EDNO介导的糖尿病动脉舒张功能因内皮源性自由基产生增加而受损。超氧化物歧化酶（一种超氧阴离子清除剂）和二甲基硫脲（一种羟基自由基清除剂）使糖尿病动脉中EDNO介导的舒张正常化。对于未处理的和SOD-和DMTU-处理的糖尿病动脉，乙酰胆碱的艾德（50）值分别为13.5、5.5和4 nM（处理的与未处理的动脉相比，P < 0.05）。超氧阴离子和羟基自由基似乎通过灭活EDNO来阻断EDNO介导的舒张。EDNO重要的血管保护特性的丧失可能作为糖尿病血管疾病及其随后并发症的产生的重要起始机制。
Diabetes was induced in rats by an injection of streptozotocin (55 mg/kg). Endothelium-dependent relaxations in mesenteric resistance arteries (luminal diameter 210 +/- 20 mu m) of control and diabetic rats were compared in myographs. Acetylcholine induced endothelium-dependent relaxations that were mediated by nitric oxide (EDNO). EDNO-mediated relaxations were impaired in diabetic arteries; concentrations of acetylcholine required to produce 50% relaxation (ED(50)) of activated arteries were 5 nM in control and 13.5 nM in arteries from diabetic rats studied after 6 wk (P < 0.05). The impairment in relaxation worsened with duration of the diabetes; ED(50) for acetylcholine increased to 63 and 100 nM in diabetic arteries studied after 16 and 24 wk of diabetes, respectively. NG-nitro-L-arginine produced 5.5- and 16-fold decreases in sensitivity of control and diabetic arteries to acetylcholine. NG-nitro-L-arginine produced at least as much inhibition of acetylcholine relaxations in diabetic arteries, indicating that the impaired relaxation noted in diabetic arteries does not result from decreased production of EDNO. EDNO-mediated relaxations in diabetic arteries were impaired by increased production of endothelium-derived free radicals. Superoxide dismutase, a scavenger of superoxide anion, and dimethylthiourea, a scavenger of hydroxyl radicals, normalized EDNO-mediated relaxations in diabetic arteries. The ED(50) values for acetylcholine were 13.5, 5.5, and 4 nM for untreated and SOD- and DMTU-treated diabetic arteries, respectively (P < 0.05 for treated vs. untreated arteries). Superoxide anion and hydroxyl radicals appear to block EDNO-mediated relaxation by inactivating EDNO. Loss of the important vasoprotective properties of EDNO may serve as an important initiating mechanism in the production of diabetic vascular disease and its ensuing complications.