The in vivo effect of endothelins on retinal circulation in nondiabetic and diabetic rats.
The in vivo effect of endothelins on retinal circulation in nondiabetic and diabetic rats.
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DOI：
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发表时间：
1995-03
影响因子：
4.4
通讯作者：
S. Bursell;A. Clermont;B. Oren;G. L. King
中科院分区：
文献类型：
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作者：
S. Bursell;A. Clermont;B. Oren;G. L. King
目的内皮素是一种有效的血管活性肽。本研究旨在探讨内皮素肽对非糖尿病大鼠和糖尿病大鼠视网膜循环的影响。方法采用视频荧光素血管造影方法，定量观察大鼠视网膜对内皮素-1 （ET-1）和内皮素-3 （ET-3）的血流动力学反应。实验共使用99只大鼠。在非糖尿病大鼠和糖尿病大鼠玻璃体内注射不同浓度ET-1和ET-3之前和之后的不同时间进行荧光素血管造影录像记录。利用计算机辅助图像分析记录的血管造影，确定血管直径和视网膜循环时间。结果ET-1的最大反应出现在玻璃体内注射后15分钟，并持续30分钟。玻璃体内注射后15分钟测量的数据显示视网膜循环时间明显延长，视网膜动脉收缩。例如，在浓度为10(-7)M时，视网膜循环时间增加了基线值的270% +/- 121%。相比之下，注射10(-7)M ET-3的循环时间比基线增加了52% +/- 29.5%。在糖尿病动物中，与在非糖尿病大鼠中注射相同浓度的ET-1相比，注射10(-7)M ET-1显示出钝化反应（仅为基线的26% +/- 8%）。结论：大鼠视网膜循环对ET-1玻璃体内注射有明显的视网膜反应。ET-3的反应明显低于ET-1，糖尿病动物的视网膜对ET-1的反应也明显减弱。对ET-3的迟钝反应与视网膜血管ET-1受体对ET-3的亲和力较低一致。糖尿病大鼠的ET-1反应减弱与先前报道的结果一致，表明暴露于高葡萄糖的视网膜周细胞对ET-1作用具有抗性。
PURPOSE The endothelins are potent vasoactive peptides. This study was performed to characterize the in vivo effects of the endothelin peptides on the retinal circulation in nondiabetic and diabetic rats. METHODS The video fluorescein angiography methodology was used to quantitate retinal hemodynamic responses to endothelin-1 (ET-1) and endothelin-3 (ET-3) in rats. A total of 99 rats were used for these experiments. Video fluorescein angiography recordings were performed before and at different times after intravitreal injection of different concentrations of ET-1 and ET-3 in nondiabetic and diabetic rats. Vascular diameters and retinal circulation times were determined using computer-assisted image analysis of the recorded angiograms. RESULTS The maximal response to ET-1 was observed at 15 minutes after intravitreal injection and was maintained for as long as 30 minutes after injection. Subsequent data measured at 15 minutes after intravitreal injection showed significant prolongation of retinal circulation times and retinal artery constriction. For example, at a concentration of 10(-7) M, the retinal circulation time increased by 270% +/- 121% of the baseline value. In contrast, 10(-7) M ET-3 injection showed a 52% +/- 29.5% increase in circulation time compared to baseline. In diabetic animals, 10(-7) M ET-1 injection showed a blunted response (only 26% +/- 8% of baseline) compared to the same ET-1 injected concentration in nondiabetic rats. CONCLUSIONS The rat retinal circulation shows a pronounced retinal response to ET-1 intravitreal injection. The response to ET-3 is significantly less than it is to ET-1, and in diabetic animals there was also a significant blunting of the retinal response to ET-1. The blunted response to ET-3 is consistent with the lower affinity of retinal vessel ET-1 receptors to ET-3. The blunted ET-1 response in diabetic rats is consistent with previously reported results, demonstrating resistance to ET-1 action in retinal pericytes exposed to high glucose.