PURPOSE:To characterize the role of the endothelin system in the blood flow control of the optic nerve head and of the choroid in humans. METHODS:Two studies were performed in healthy subjects. Study 1 was a randomized, placebo-controlled, double-masked, balanced, two-way crossover design and study 2 a three way-way crossover design. In study 1 twelve healthy male subjects received endothelin (ET)-1 in stepwise increasing doses of 1.25, 2.5, and 5 ng/kg x min (each infusion step occurred over 20 minutes) coinfused with BQ123 (60 microg/kg x min) or placebo on two different study days. In study 2 twelve healthy male subjects received two doses of BQ123 (60 or 120 microg/kg x min over 60 minutes) or placebo on three different study days. Measurements of optic nerve head blood flow (ONHBF) and choroidal blood flow (ChBF) were performed with laser Doppler flowmetry in both studies. In study 2 mean flow velocity (MFV) of the ophthalmic artery was assessed with Doppler sonography. RESULTS:In study 1, ET-1 significantly decreased ONHBF (-22.8% +/- 4.3% at 5 ng/kg x min, P = 0.003 versus baseline) and ChBF (-21.7% +/- 3.2% at 5 ng/kg x min, P = 0.0001 versus baseline). The effect of the highest administered dose of exogenous ET-1 on ONHBF was significantly attenuated (P = 0.04, ANOVA) by coinfusion of BQ123. Effects of exogenous ET-1 on blood flow (2.5 ng/kg x min ET-1 or higher) also were attenuated in the choroid by coinfusion of BQ123 (ChBF: P = 0.03, ANOVA). In study 2, both dosages of BQ123 significantly increased MFV in the ophthalmic artery (60 microg/kg x min, 12.5% +/- 7.3%; 120 microg/kg x min, 17.2% +/- 9.2%, versus baseline; P = 0.001), but did not change blood flow in the ONH or the choroid. CONCLUSIONS:BQ123 antagonizes the effects of exogenously administered ET-1 on blood flow in the ONH and the choroid. The data indicate, however, that ET-1 does not substantially contribute to the regulation of basal vascular tone in these tissues.

译文

目的:表征内皮素系统在人类视神经乳头和脉络膜的血流控制中的作用。
方法:在健康受试者中进行了两项研究。研究1是随机的,安慰剂对照,双掩蔽,平衡的两向交叉设计,而研究2是三向交叉设计。在研究1中,十二名健康男性受试者分别以1.25、2.5和5 ng / kg x min的剂量逐步增加剂量接受内皮素(ET)-1(每个输注步骤发生在20分钟之内),并与BQ123(60 microg / kg x min)混合或在两个不同的学习日服用安慰剂。在研究2中,十二位健康的男性受试者在三个不同的研究日接受了两剂BQ123(60分钟内60或120 microg / kg x分钟)或安慰剂。在这两项研究中,均使用激光多普勒血流仪对视神经乳头血流量(ONHBF)和脉络膜血流量(ChBF)进行了测量。在研究2中,用多普勒超声检查评估了眼动脉的平均流速(MFV)。
结果:在研究1中,ET-1显着降低了ONHBF(5 ng / kg x min时为-22.8%/-4.3%,相对于基线P = 0.003)和ChBF(5 ng / kg x时为-21.7%/-3.2%)最小值,相对于基线,P = 0.0001)。 BQ123的共融合显着减轻了最高剂量的外源ET-1对ONHBF的影响(P = 0.04,ANOVA)。 BQ123的共融合也减轻了脉络膜中外源性ET-1对血流的影响(2.5 ng / kg x min ET-1或更高)(ChBF:P = 0.03,ANOVA)。在研究2中,两种BQ123剂量均显着增加了眼动脉中的MFV(与基线相比,分别为60微克/千克x分钟,12.5%/-7.3%; 120微克/千克x分钟,17.2%/-9.2%; P = 0.001 ),但没有改变ONH或脉络膜中的血流。
结论:BQ123拮抗外源性ET-1对ONH和脉络膜中血流的影响。然而,数据表明,ET-1在这些组织中基本无助于调节基础血管张力。

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