Regulation of human retinal blood flow by endothelin-1
Regulation of human retinal blood flow by endothelin-1
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DOI：
10.1016/s0014-4835(02)00312-3
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Schmetterer, L
中科院分区：
文献类型：
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作者：
Polak, K;Luksch, A;Schmetterer, L
体外和动物研究的证据表明内皮素是视网膜血流的主要调节剂。我们着手描述内皮素系统在人类视网膜血流控制中的作用。对健康受试者进行了两项研究。研究设计为随机、安慰剂对照、双盲、平衡、方案A中的双向交叉和方案B中的三路交叉。在方案A中，18名健康男性受试者以2.5ng·kg(-1)·min(-1)的剂量静脉注射内皮素-1(ET-1)30分钟，或在两个不同的研究日接受安慰剂，并测量视网膜血管直径。在方案 B 中，12 名健康男性受试者接受 ET-1，逐步增加剂量 0、1.25、2.5 和 5 ng kg(-1) min(-1)（每次输注步骤超过 20 分钟），与特定 ETA 受体拮抗剂 BQ123（60 杯 min(-1)）或安慰剂或单独 BQ123 共同输注，研究视网膜血管直径、视网膜血流速度和视网膜血流量。使用蔡司视网膜血管分析仪测量视网膜血管尺寸。血流速度的测量是通过双向激光多普勒测速仪进行的。根据这些测量结果计算视网膜血流量。在方案A中，外源性ET-1倾向于减小视网膜动脉直径，但与安慰剂相比，这种效果并不显着。未观察到对视网膜静脉直径的影响。在方案B中，给予外源性ET-1后，视网膜静脉血流速度和视网膜血流量显着降低。当同时服用 BQ-123 时，这些作用显着减弱。相比之下，单独使用 BQ-123 对视网膜血流动力学参数没有影响。结论是，BQ123 拮抗外源性施用 ET-1 对健康受试者视网膜血流的影响。此外，本研究的结果与ET-1在视网膜中主要在微血管上发挥其血管收缩作用的假设相一致。 (C) 2003 Elsevier Science Ltd. 保留所有权利。
There is evidence from in vitro and animal studies that endothelin is a major regulator of retinal blood flow. We set out to characterize the role of the endothelin-system in the blood flow control of the human retina. Two studies in healthy subjects were performed. The study design was randomized, placebo-controlled, double-masked, balanced, two-way crossover in protocol A and three way-way crossover in protocol B. In protocol A 18 healthy male subjects received intravenous endothelin-1 (ET-1) in a dose of 2.5 ng kg(-1) min(-1) for 30 min or placebo on two different study days and retinal vessel diameters were measured. In protocol B 12 healthy male subjects received ET-1 in stepwise increasing doses of 0, 1.25, 2.5 and 5 ng kg(-1) min(-1) (each infusion step over 20 min) in co-infusion with the specific ETA-receptor antagonist BQ123 (60 mug min(-1)) or placebo or BQ123 alone investigating retinal vessel diameters, retinal blood velocity and retinal blood flow. Measurements of retinal vessel size were done with the Zeiss retinal vessel analyzer. Measurements of blood velocities were done with bi-directional laser Doppler velocimetry. From these measurements retinal blood flow was calculated. In protocol A exogenous ET-1 tended to decrease retinal arterial diameter, but this effect was not significant versus placebo. No effect on retinal venous diameter was seen. In protocol B retinal venous blood velocity and retinal blood flow was significantly reduced after administration of exogenous ET-1. These effects were significantly blunted when BQ-123 was co-administered. By contrast, BQ-123 alone had no effect on retinal hemodynamic parameters. Concluding, BQ123 antagonizes the effects of exogenously administered ET-1 on retinal blood flow in healthy subjects. In addition, the results of the present study are compatible with the hypothesis that ET-1 exerts its vasoconstrictor effects in the retina mainly on the microvessels. (C) 2003 Elsevier Science Ltd. All rights reserved.