Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
Invest Ophthalmol Vis Sci. 2010 May;51(5):2648-55. doi: 10.1167/iovs.09-4070. Epub 2009 Dec 30.
To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia.
Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment.
The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P < 0.05) inhibited by acute hyperglycemia. TEMPOL significantly (P < 0.05) prevented a decrease in the BK-induced increase in RBF during hyperglycemia.
The results suggest that acute hyperglycemia increases RBF via increased osmolality and may cause retinal endothelial dysfunction partially via increased oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.
研究急性高血糖对猫视网膜微循环和内皮功能的影响，并去除超氧阴离子以防止高血糖引起的视网膜内皮功能障碍。
通过静脉注射 25%葡萄糖将血糖维持在 30mM，诱导高血糖。使用激光多普勒流速计同时测量血管直径（D）和血流速度（V），计算猫二级视网膜动脉的视网膜血流（RBF）。向玻璃体腔内注射内皮依赖性血管扩张剂缓激肽（BK）和内皮非依赖性血管扩张剂硝普钠（SNP），以评估视网膜小动脉的内皮功能。为了控制渗透压，以同样的方式给予 25%甘露醇。通过诱导全身高氧血症，在高血糖期间非侵入性地检查内皮功能。为了确定超氧阴离子对高血糖引起的视网膜循环变化的影响，在实验前 14 天通过饮用水给予 4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基（TEMPOL）。
与基线相比，D、V 和 RBF 在急性高血糖和甘露醇作用下增加。BK 诱导的 D、V 和 RBF 增加明显下降，而 SNP 诱导的增加在急性高血糖期间未减弱。在停止全身高氧血症后，BK 诱导的 RBF 恢复到基线的速度明显（P<0.05）受到急性高血糖的抑制。TEMPOL 显著（P<0.05）防止了高血糖期间 BK 诱导的 RBF 减少。
这些结果表明，急性高血糖通过增加渗透压增加 RBF，并且可能部分通过增加氧化应激引起视网膜内皮功能障碍。全身高氧血症可用于非侵入性地评估高血糖期间的视网膜内皮功能。
