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Partial Antagonism of Endothelin 1–Induced Vasoconstriction in the Human Choroid by Topical Unoprostone Isopropyl
Elzbieta Polska, MD;
Arno Doelemeyer, MSc;
Alexandra Luksch, MD;
Paulina Ehrlich, MD;
Nils Kaehler, MD;
Christine L. Percicot, MD;
George N. Lambrou, MD;
Leopold Schmetterer, PhD
Arch Ophthalmol. 2002;120:348-352.
Background There is increasing evidence that reduced ocular blood flow plays a
role in the pathogenesis of glaucoma. In patients with normal-tension glaucoma,
ocular blood flow abnormalities may be associated with dysfunction of the
endothelin 1 (ET-1) regulation system.
Objective To test the hypothesis that unoprostone, a topical docosanoid, may affect
ET-1–induced vasoconstriction in the human choroid.
Methods In a placebo-controlled, randomized, double-masked, 2-way crossover
design, ET-1 (2.5 ng/kg per minute for 150 minutes) was administered intravenously
to 24 healthy individuals. Thirty minutes after the start of ET-1 infusion,
1 drop of unoprostone or placebo was instilled into the right eye. After another
30 minutes, 2 drops of unoprostone or placebo was topically administered.
This procedure was continued and the dose was increased further until 4 drops
of unoprostone or placebo was reached. Subfoveal and pulsatile choroidal blood
flow were assessed using laser Doppler flowmetry and laser interferometric
measurement of fundus pulsation amplitude, respectively.
Results Administration of exogenous ET-1 decreased choroidal blood flow (mean
± SEM, 17% ± 2%; P<.001) and fundus pulsation
amplitude (mean ± SEM, 19% ± 2%; P<.001).
This effect was significantly blunted when topical unoprostone was coadministered
(mean ± SEM decrease in choroidal blood flow, 7% ± 2%; P = .04 vs placebo; mean ± SEM decrease in fundus
pulsation amplitude, 12% ± 2%; P<.001 vs
placebo).
Conclusion There is a functional antagonism between ET-1 and topical unoprostone
in the choroidal vasculature.
Clinical Relevance Our findings of a functional antagonism between ET-1 and topical unoprostone
in the choroidal vasculature may be important in vascular eye diseases associated
with increased ET-1.
From the Department of Clinical Pharmacology (Drs Polska, Luksch, Ehrlich,
Kaehler, and Schmetterer and Mr Doelemeyer) and the Institute of Medical Physics
(Dr Schmetterer), Vienna University, Vienna, Austria; Novartis Ophthalmics,
Basel, Switzerland (Drs Percicot and Lambrou and Mr Doelemeyer); and University
Eye Clinic, Strasbourg, France (Dr Lambrou).
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