Tetrahydrobiopterin reverses the impairment of acetylcholine-induced vasodilatation in diabetic ocular microvasculature.
Tetrahydrobiopterin reverses the impairment of acetylcholine-induced vasodilatation in diabetic ocular microvasculature.
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四氢生物蝶呤可逆转糖尿病眼部微血管中乙酰胆碱诱导的血管舒张损伤。
DOI：
10.1089/10807680151125438
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
E. Su
中科院分区：
文献类型：
--
作者：
P. Yu;D. Yu;S. Cringle;E. Su
本研究的目的是测试是否四氢生物蝶呤，一氧化氮合成的重要辅助因子，可以逆转糖尿病眼循环内皮功能障碍。使用链脲佐菌素诱导的糖尿病大鼠模型和离体灌注眼技术，对乙酰胆碱（一种由刺激的一氧化氮释放介导的内皮依赖性血管扩张剂）诱导的糖尿病眼血管舒张反应进行了比较，之前和之后的四氢生物蝶呤管理。年龄匹配的正常大鼠用于参考响应。分别在诱导后21.5 +/- 0.2周和21.2 +/- 2.1周使用6只链脲佐菌素诱导的糖尿病大鼠和11只对照大鼠。发现糖尿病眼的剂量反应曲线与对照眼显著不同（p < 0.001），对10（-4）M乙酰胆碱的反应显著降低。然而，在对糖尿病眼睛施用四氢生物蝶呤30分钟后，与施用四氢生物蝶呤之前的反应相比，乙酰胆碱诱导的血管舒张反应显著增加（p < 0.001）。四氢生物蝶呤给药后糖尿病患者眼睛的血管舒张反应水平与对照反应相当（p = 0.742）。我们已经证明，在诱导后21.5 +/- 0.2周，急性给予四氢生物蝶呤可有效地将受损的乙酰胆碱诱导的血管舒张反应逆转至对照水平。我们的研究结果表明，四氢生物蝶呤在链脲佐菌素诱导的糖尿病大鼠的眼睛水平下降可能是负责眼血管内皮功能障碍。
The purpose of this study is to test whether tetrahydrobiopterin, an essential cofactor in nitric oxide synthesis, can reverse endothelium dysfunction in diabetic ocular circulation. Using the streptozotocin-induced diabetic rat model and the isolated perfusion eye technique, the response to the acetylcholine (an endothelium-dependent vasodilator mediated by stimulated nitric oxide release) induced vasodilatation of the diabetic ocular vasculature before and after tetrahydrobiopterin administration was compared. Age matched normal rats were used for reference response. Six streptozotocin-induced diabetic rats and eleven control rats at 21.5 +/- 0.2 weeks and 21.2 +/- 2.1 weeks postinduction, respectively, were used. The dose response curve from the diabetic eyes was found to be significantly different from that of the control eyes (p < 0.001) with significantly reduced responses to 10(-4)M acetylcholine. After 30 min of administration of tetrahydrobiopterin to the diabetic eyes, however, the acetylcholine-induced vasodilatation response was significantly (p < 0.001) increased compared with the response prior to tetrahydrobiopterin administration. The vasodilatory response in the diabetic eyes after tetrahydrobiopterin administration was at a level that was comparable with the control response (p = 0.742). We have shown that acute administration of tetrahydrobiopterin is effective in reversing to control level the impaired acetylcholine-induced vasodilatory response at 21.5 +/- 0.2 weeks postinduction. Our result suggests that a decreased level of tetrahydrobiopterin in the eyes of the streptozotocin-induced diabetic rats may be responsible for the ocular vascular endothelium dysfunction.
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影响因子：
4.4
作者：
C. Riva;J. Grunwald;S. Sinclair;B. Petrig
通讯作者：
C. Riva;J. Grunwald;S. Sinclair;B. Petrig
四氢生物蝶呤是一氧化氮合酶的辅助因子，可产生小鼠软脑膜小动脉的内皮依赖性扩张。
影响因子：
8.3
作者：
Rosenblum,WI
通讯作者：
Rosenblum,WI
通过增加内皮素-1 的表达和作用来调节糖尿病大鼠的视网膜血流动力学。
影响因子：
4.4
作者：
Takagi,C;Bursell,SE;Lin,YW;Takagi,H;Duh,E;Jiang,Z;Clermont,AC;King,GL
通讯作者：
King,GL
影响因子：
3.4
作者：
McLenachan, Samuel;Magno, Aaron Len;Ruberte, Jesus
通讯作者：
Ruberte, Jesus