Impaired retinal vasodilator response to acetylcholine in a rat model of NMDA-induced retinal degeneration.
Impaired retinal vasodilator response to acetylcholine in a rat model of NMDA-induced retinal degeneration.
复制标题
NMDA 诱导的视网膜变性大鼠模型中视网膜血管舒张剂对乙酰胆碱的反应受损。
DOI：
10.1016/j.jphs.2014.12.014
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Ishii K.
中科院分区：
文献类型：
--
作者：
Mori A;Hanada M;Sakamoto K;Nakahara T;Ishii K.
先前的研究表明，N-甲基-d-天冬氨酸（NMDA）诱导的视网膜神经毒性后会发生视网膜毛细血管变性，但尚不清楚视网膜血管的舒张机制是否发生改变。本研究的目的是确定 NMDA 诱导的视网膜损伤大鼠模型中视网膜血管舒张反应是否受到影响。单次玻璃体内注射 NMDA（200 nmol）后 14 天，通过测量眼底图像中视网膜小动脉的直径来评估视网膜血管舒张反应。在 NMDA 处理的视网膜中，乙酰胆碱诱导的视网膜小动脉血管舒张显着减少，而一氧化氮 (NO) 供体 NOR3、β2-肾上腺素受体激动剂沙丁胺醇和 β3-肾上腺素受体激动剂 CL316243 的视网膜血管舒张作用没有改变。在使用 NG-硝基-L-精氨酸甲酯（30 mg/kg，静脉注射）加吲哚美辛（5 mg/kg，静脉注射）联合阻断 NO 合酶和环氧合酶的情况下观察到的对乙酰胆碱的血管舒张反应（可能是内皮源性超极化因子介导的反应）也有所降低。这些结果表明，在 NMDA 诱导的视网膜变性大鼠模型中，视网膜血管中内皮依赖性血管舒张机制受到损害。谷氨酸引起的神经毒性与多种视网膜疾病有关。因此，视网膜循环异常会促进疾病的进展。
Previous studies have shown that degeneration of retinal capillaries occurs followingN-methyl-d-aspartate (NMDA)-induced retinal neurotoxicity, but it is unclear whether vasodilatory mechanisms are altered in retinal blood vessels. The purpose of the present study was to determine whether retinal vasodilator responses are affected in a rat model of NMDA-induced retinal damage. At 14 days after a single intravitreal injection of NMDA (200 nmol), retinal vasodilator responses were assessed by measuring the diameter of retinal arterioles in fundus images. Acetylcholine-induced vasodilation of retinal arterioles was significantly reduced in NMDA-treated retinas, whereas retinal vasodilatory effects of the nitric oxide (NO) donor NOR3, the β2-adrenoceptor agonist salbutamol, and the β3-adrenoceptor agonist CL316243 were unaltered. The vasodilator response to acetylcholine observed under the combined blockade of NO synthase and cyclooxygenase with NG-nitro-l-arginine methyl ester (30 mg/kg, i.v.) plus indomethacin (5 mg/kg, i.v.), possibly an endothelium-derived hyperpolarizing factor-mediated response, was also reduced. These results suggest that endothelium-dependent vasodilatory mechanisms in retinal blood vessels are impaired in the rat model of NMDA-induced retinal degeneration. Glutamate-induced neurotoxicity is implicated in several retinal diseases; therefore, abnormal retinal circulation would contribute to the progression of the diseases.