内皮素对非糖尿病和糖尿病大鼠视网膜循环的体内作用。

The in vivo effect of endothelins on retinal circulation in nondiabetic and diabetic rats.

作者信息

Bursell S E, Clermont A C, Oren B, King G L

机构信息

Beetham Eye Institute/Joslin Diabetes Center, Boston, MA 02215.

出版信息

Invest Ophthalmol Vis Sci. 1995 Mar;36(3):596-607.

PMID:7890491

Abstract

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.

摘要

目的

内皮素是强效血管活性肽。本研究旨在表征内皮素肽对非糖尿病和糖尿病大鼠视网膜循环的体内作用。

方法

采用视频荧光血管造影术来定量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。总共99只大鼠用于这些实验。在非糖尿病和糖尿病大鼠玻璃体内注射不同浓度的ET-1和ET-3之前及之后的不同时间进行视频荧光血管造影记录。使用计算机辅助图像分析记录的血管造影片来确定血管直径和视网膜循环时间。

结果

玻璃体内注射后15分钟观察到对ET-1的最大反应，并在注射后长达30分钟保持。玻璃体内注射后15分钟测量的后续数据显示视网膜循环时间显著延长和视网膜动脉收缩。例如，在浓度为10^(-7) M时，视网膜循环时间比基线值增加了270%±121%。相比之下，注射10^(-7) M ET-3显示循环时间比基线增加了52%±29.5%。在糖尿病动物中，与非糖尿病大鼠注射相同浓度的ET-1相比，注射10^(-7) M ET-1显示反应减弱（仅为基线的26%±8%）。

结论

大鼠视网膜循环对玻璃体内注射ET-1表现出明显的视网膜反应。对ET-3的反应明显小于对ET-1的反应，并且在糖尿病动物中，视网膜对ET-1的反应也明显减弱。对ET-3的反应减弱与视网膜血管ET-1受体对ET-3的较低亲和力一致。糖尿病大鼠中ET-1反应减弱与先前报道的结果一致，表明暴露于高血糖的视网膜周细胞对ET-1作用具有抗性。