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PURPOSE: To characterize the role of the endothelin system in blood flow control of the optic nerve head (ONH) and choroid in humans. METHODS: Two studied 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 crossover design. In study 1, 12 healthy male subjects received endothelin (ET)-1 in stepwise increasing doses of 1.25, 2.5, and 5 ng/kg·min (each infusion step occurred over 20 minutes), co-infused with BQ123 (60 μg/kg·min) or placebo on two different study days. In study 2, 12 healthy male subjects received two doses of BQ123 (60 or 120 μg/kg·.min over 60 minutes) or placebo on three different study days. Measurements of ONH 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 ng/kg·min, p - 0.003 versus baseline) and ChBF (021.7 ± 3.2% at 5 ng/kg·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 co-infusion of BQ123. Effects of exogenous ET-1 on blood flow (2.5 ng/kg·min ET-1 or higher) were also attenuated in the choroid by co-infusion of BQ123 (ChBF: p = 0.03, ANOVA). In study 2, both dosages of BQ123 significantly increased MFV in the ophthalmic artery (60 μg/kg·min, 12.5 ± 7.3%; 120 μg/kg·min, 17.2 ± 9.2%, versus baseline; p = 0.001), but did not change blood flow in the ONH or choroid. CONCLUSIONS: BQ123 antagonizes the effects of exogenously administered ET-1 on blood flow in the ONH and choroid. However, the data indicate that ET-1 does not substantially contribute to the regulation of basal vascular tone in these tissues.
Dr L. Schmetterer, Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Währinger Gürtel 18-20, A-1090 Vienna, Austria. leopold.schmetterer@univie.ac.at
6.8.2 Posterior segment (Part of: 6 Clinical examination methods > 6.8 Photography)