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Kaija Polak, Vanessa Petternel, Alexandra Luksch, Joachim Krohn, Oliver Findl, Elzbieta Polska, Leopold Schmetterer; Effect of Endothelin and BQ123 on Ocular Blood Flow Parameters in Healthy Subjects. Invest. Ophthalmol. Vis. Sci. 2001;42(12):2949-2956.
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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 · min (each
infusion step occurred over 20 minutes) coinfused with BQ123 (60μ
g/kg · min) or placebo on two different study days. In study 2
twelve healthy male subjects received two doses of BQ123 (60 or 120μ
g/kg · 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 · 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 coinfusion of BQ123. Effects
of exogenous ET-1 on blood flow (2.5 ng/kg · 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 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 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.
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