Effect of endothelin and BQ123 on ocular blood flow parameters in healthy subjects

Purpose. To characterize the role of the endothelin system in the blood flo w control of the optic nerve head and of the choroid in humans. Methods. Two studies were performed in healthy subjects. Study 1 was a rand omized, placebo-controlled, double-masked, balanced, two-way crossover desi gn and study 2 a three way-way crossover design. In study I twelve 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) coin fused with BQ123 (60 mug/kg.min) or placebo on two different study days. In study 2 twelve healthy male subjects received two doses of BQ123 (60 or 12 0 mug/kg.min over 60 minutes) or placebo on three different study days. Mea surements 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 Dopp ler sonography. Results. In study 1, ET-1 significantly decreased ONHBF (-22.8%+/-4.3% at 5 ng/kg.min, P=0.003 versus baseline) and ChBF (-21.7%+/-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 E T-I 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 incre ased MFV in the ophthalmic artery (60 mug/kg.min, 12.5%+/-7.3%; 120 mug/kg. 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.