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Effect of Avosentan (SSP-301) in Porcine Ciliary Arteries

Konieczka, Katarzyna and Meyer, Peter and Schoetzau, Andreas and Neutzner, Albert and Mozaffarieh, Maneli and Flammer, Josef (2011) Effect of Avosentan (SSP-301) in Porcine Ciliary Arteries. Current Eye Research, 36 (2). pp. 118-124. ISSN 0271-3683

Abstract

Purpose: To investigate the vasoactive effect of ETA– endothelin receptor antagonist avosentan (SPP-301) and other ETA – endothelin receptor antagonist BQ-123 in isolated porcine ciliary arteries with and without endothelium. To investigate the effect of avosentan on the endothelin-1 induced contractions in comparison with BQ-123 and BQ-788 (ETB - endothelin receptor antagonist) in isolated porcine ciliary arteries with and without endothelium.
Methods: Vessels were placed in a myograph system to measure isometric forces. In a first set of experiments quiescent vessels were exposed, cumulatively, to increasing concentrations of avosentan and BQ-123 (10-9M – 3x10-6M). In a second set of experiments quiescent vessels were first incubated with avosentan (10-6M and 10-8M), BQ-123 (10-6M) and BQ-788 (10-6M), respectively. Then the vessels were exposed, cumulatively, to increasing concentrations of endothelin-1 (10-12M – 3x10-8M). Each set of experiments was conducted in the vessels with and without endothelium.
Results: Cumulative doses of avosentan and BQ-123 had no vasoactive effect in quiescent vessels. Avosentan had a strong inhibitory effect on the endothelin-1 induced contractions. The inhibitory effect of 10-6M avosentan was significantly stronger than the effect of 10-8M avosentan. The effect of avosentan (10-6M) tended to be stronger than the effect of BQ-123 (10-6M). To a lesser extent BQ- 788 also had inhibitory effect on the endothelin-1 induced contractions.
Conclusions: Avosentan has a strong inhibitory effect on the endothelin-1 induced contractions. Blockade of ET receptors is an attractive target in many eye diseases including laucoma. Further studies are needed to evaluate the usefulness of endothelin blockers in ophthalmology.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2900

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