Hyperglycemia Accelerates Impairment of Vasodilator Responses to Acetylcholine of Retinal Blood Vessels in Rats
Hyperglycemia Accelerates Impairment of Vasodilator Responses to Acetylcholine of Retinal Blood Vessels in Rats
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DOI：
10.1254/jphs.08320fp
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发表时间：
2009-06-01
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
我们以前曾报道，链脲佐菌素(STZ)诱导大鼠高血糖6-8周后，视网膜和全身循环中的血管内皮功能受损。然而，根据血管床和高血糖的严重程度，内皮功能障碍发生所需的时间是否不同仍有待阐明。在这项研究中，我们观察了几种血管扩张剂对对照组、STZ(STZ单独治疗)和STZ+GLC(STZ治疗+D-葡萄糖喂养)大鼠视网膜血管内径和血压的影响。对视网膜和视网膜毛细血管网络的整体结构也进行了评估。诱导高血糖2周后，STZ+GLC组视网膜小动脉的血管扩张作用明显减弱，而STZ组无明显变化。在乙酰胆碱诱导的血压下降方面，三个实验组之间没有显著差异。对NOR3、Forskolin和腺苷的反应不受高血糖的影响。STZ+GLC组视网膜厚度明显减少。免疫组织化学方法显示视网膜毛细血管网形态和密度无明显变化。这些结果表明，视网膜小动脉的内皮依赖性血管扩张机制比外周阻力血管更容易受到高血糖的影响。根据视网膜内皮功能障碍的严重程度，高血糖可缩短视网膜内皮功能障碍的发病时间。
We previously reported that vascular endothelial functions in both retinal and systemic circulation are impaired 6 - 8 weeks after induction of hyperglycemia with streptozotocin (STZ) in rats. However, it remains to be elucidated whether the period required for the onset of endothelial dysfunction is different, depending on vascular beds and severity of hyperglycemia. In this Study, we examined the effects of several vasodilators on the diameter of retinal blood vessel and blood pressure in Control, STZ (STZ treatment alone), and STZ + Glc (STZ treatment plus D-glucose feeding rats. The overall structures of the retina and the retinal capillary network were also evaluated. The vasodilator effects of acetylcholine on retinal arterioles were significantly reduced in the STZ + Glc group, but not in the STZ group, 2 weeks after induction of hyperglycemia. There were no significant differences in acetylcholine-induced decreases in blood pressure among the three experimental groups. The responses to NOR3, forskolin, and adenosine were unaffected by hyperglycemia. The retinal thickness was significantly reduced in the STZ + Glc group. No significant changes were observed in the morphology and the density of retinal capillary network by immunohistochemical techniques. These results suggest that endothelium-dependent vasodilatory mechanisms of retinal arterioles are more vulnerable than those of peripheral resistance vessels to the effects of hyperglycemia. Hyperglycemia shortens the period required for onset of retinal endothelial dysfunction, depending on its severity.