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Abstract #6840 Published in IGR 4-1
Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl
Polska E; Doelemeyer A; Luksch A; Ehrlich P; Kaehler N; Percicot CL; Lambrou GN; Schmetterer LArchives of Ophthalmology 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, two-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, one drop of unoprostone or placebo was instilled into the right eye. After another 30 minutes, two drops of unoprostone or placebo were topically administered. This procedure was continued and the dose was increased further until four 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 < 0.001) and fundus pulsation amplitude (mean ± SEM, 19% ± 2%; p < 0.001). This effect was significantly blunted when topical unoprostone was coadministered (mean ± SEM decrease in choroidal blood flow, 7% ± 2%; p = 0.04 versus placebo; mean ± SEM decrease in fundus pulsation amplitude, 12% ± 2%; p < 0.001 versus placebo). CONCLUSION: There is a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature. CLINICAL RELEVANCE: These 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.
Dr. E. Polska, Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
