Hyperglycemia Impairs Acetylcholine-Induced Vasodilation of Retinal Arterioles Through Polyol Pathway-Independent Mechanisms in Rats
Hyperglycemia Impairs Acetylcholine-Induced Vasodilation of Retinal Arterioles Through Polyol Pathway-Independent Mechanisms in Rats
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DOI：
10.1254/jphs.09312fp
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发表时间：
2010-03-01
影响因子：
3.5
通讯作者：
Ishii, Kunio
中科院分区：
文献类型：
--
作者：
Mori, Asami;Saigo, Orie;Ishii, Kunio
我们之前报道过，糖尿病大鼠中乙酰胆碱（ACh）诱导的视网膜小动脉血管舒张作用减弱；然而，这种现象的根本机制尚未完全阐明。为了确定多元醇途径在糖尿病引起的视网膜血管功能障碍中的作用，我们研究了醛糖还原酶抑制剂 GP-1447 对减弱糖尿病大鼠中乙酰胆碱诱导的视网膜小动脉血管舒张的作用。雄性 Wistar 大鼠接受链脲佐菌素 (STZ) 治疗，两周后进行实验。 STZ治疗的动物被给予含有5％D-葡萄糖的饮用水，以缩短视网膜血管功能障碍的发展期限。 STZ 治疗后立即开始 GP-1447 治疗，并持续整个 2 周的实验期。 GP-1447 治疗并未改变视网膜血管对乙酰胆碱反应的减弱，而醛糖还原酶抑制剂完全阻止了糖尿病引起的视网膜变薄以及山梨醇在视网膜和晶状体中的积聚。这些结果表明，独立于多元醇途径的机制可能导致视网膜内皮功能障碍的发生，尽管该途径在糖尿病大鼠视网膜形态变化和白内障形成中发挥重要作用。
We previously reported that acetylcholine (ACh) induced vasodilation of retinal arterioles is diminished in diabetic rats; however, the underlying mechanism(s) of this phenomenon has not been fully elucidated. To determine the role of the polyol pathway in the diabetes-induced retinal vascular dysfunction, we investigated the effect of GP-1447, an inhibitor of aldose reductase, on the attenuation of ACh-induced vasodilation of retinal arterioles seen in diabetic rats. Male Wistar rats were treated with streptozotocin (STZ) and experiments were performed 2 weeks later. The STZ-treated animals were given drinking water containing 5% D-glucose to shorten the term for the development of retinal vascular dysfunction. Treatment with GP-1447 was initiated immediately after STZ treatment and continued throughout the 2-week experimental period. The attenuation of retinal vascular responses to ACh were not modified by treatment with GP-1447, whereas the aldose reductase inhibitor completely prevented diabetes-induced thinning of the retina and sorbitol accumulation in the retina and the lens. These results suggest that mechanisms that are independent of the polyol pathway may contribute to the onset of retinal endothelial dysfunction, although the pathway plays an important role in morphological changes of retina and formation of cataracts in diabetic rats.