Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Exp Eye Res. 2010 Nov;91(5):670-5. doi: 10.1016/j.exer.2010.08.008. Epub 2010 Aug 19.
Hyperglycemia mediates endothelial cell dysfunction through a number of potential mechanisms that could result in the decrease of retinal blood flow early in diabetes. The aim of this study was to explore the role of endothelin receptor A (ET(A)) in the early decrease of retinal blood flow in diabetic mice. Diabetes was induced by streptozotocin, then ∼1 wk later the mice were administered drinking water with or without the ET(A) receptor antagonist atrasentan (7.5mg/kg/day) for the following 3 weeks. Non-diabetic age-matched mice with or without atrasentan were included as controls. For each mouse, measurements of retinal vascular diameters and red blood cell (RBC) velocities were obtained via intravital microscopy for the 5-7 feed arterioles (and draining venules) extending out of (and into) the optic disk, and from these values, flow rates and wall shear rates were calculated. Additionally, the number of retinal capillaries was counted by fluorescent immunostaining of platelet-endothelial cell adhesion molecule-1 (PECAM-1). Diabetes induced statistically significant decreases in RBC velocity, flow rate, and wall shear rate, with these alterations partially inhibited by atrasentan. No changes were observed in PECAM-1 expression among groups. The changes induced by diabetes, and the attenuation provided by atrasentan, were greater in the smaller retinal arterioles. In summary, ET(A) appears to play a role in the early decreases in retinal blood flow in a mouse model of diabetes.
高血糖通过多种潜在机制介导内皮细胞功能障碍，导致糖尿病早期视网膜血流量减少。本研究旨在探讨内皮素受体 A (ET(A)) 在糖尿病小鼠早期视网膜血流量减少中的作用。通过链脲佐菌素诱导糖尿病，然后在 1 周后，给小鼠饮用含有或不含有内皮素受体拮抗剂 atrasentan（7.5mg/kg/天）的水，持续 3 周。将年龄匹配的非糖尿病小鼠和给予或不给予 atrasentan 的小鼠作为对照。对于每只小鼠，通过活体显微镜测量从视盘伸出的 5-7 条视网膜血管直径和红细胞（RBC）速度（以及引流小静脉），并从这些值计算流量和壁切率。此外，通过血小板内皮细胞黏附分子-1（PECAM-1）的荧光免疫染色计数视网膜毛细血管数。糖尿病诱导 RBC 速度、流量和壁切率的统计学显著降低，atrasentan 部分抑制了这些改变。各组之间 PECAM-1 的表达没有变化。糖尿病引起的变化以及 atrasentan 提供的衰减在较小的视网膜小动脉中更大。总之，ET(A)似乎在糖尿病小鼠模型中早期视网膜血流减少中起作用。
