title: Effect of avosentan (SPP-301) in porcine ciliary arteries.
abstract: OBJECTIVE
  To investigate the vasoactive effect of ET(A)-endothelin receptor antagonists avosentan (SPP-301) and 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 (ET(B)-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(-9) M-3 × 10(-6) M). In a second set of experiments, quiescent vessels were first incubated with avosentan (10(-6) M and 10(-8) M), BQ-123 (10(-6) M), and BQ-788 (10(-6) M), respectively. Then the vessels were exposed, cumulatively, to increasing concentrations of endothelin-1 (10(-12) M-3 × 10(-8) M). Each set of experiments was conducted in the vessels with and without endothelium.
  
  
  RESULTS
  Cumulative concentrations 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(-6) M avosentan was significantly stronger than the effect of 10(-8) M avosentan. The effect of avosentan (10(-6) M) tended to be stronger than the effect of BQ-123 (10(-6) M). To a lesser extent, BQ-788 also had an 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 potentially an attractive target in many eye diseases including glaucoma. Further studies are needed to evaluate the usefulness of endothelin blockers in ophthalmology.
authors.affiliation: Department of Ophthalmology, University of Basel, Basel, Switzerland. kkonieczka@uhbs.ch
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Konieczka
authors.forename: Peter
authors.initials: P
authors.lastname: Meyer
authors.forename: Andreas
authors.initials: A
authors.lastname: Schoetzau
authors.forename: Albert
authors.initials: A
authors.lastname: Neutzner
authors.forename: Maneli
authors.initials: M
authors.lastname: Mozaffarieh
authors.forename: Josef
authors.initials: J
authors.lastname: Flammer
mesh_terms: D000818:Animals; D019842:Ciliary Arteries / Q000187:drug effects*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D007537:Isometric Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009213:Myography; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D011725:Pyridines; D011743:Pyrimidines; C086539:BQ 788; C484919:Avosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)