title: Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl.
abstract: 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).
  
  
  CONCLUSIONS
  There is a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Polska
authors.forename: Arno
authors.initials: A
authors.lastname: Doelemeyer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Luksch
authors.forename: Paulina
authors.initials: P
authors.lastname: Ehrlich
authors.forename: Nils
authors.initials: N
authors.lastname: Kaehler
authors.forename: Christine L
authors.initials: CL
authors.lastname: Percicot
authors.forename: George N
authors.initials: GN
authors.lastname: Lambrou
authors.forename: Leopold
authors.initials: L
authors.lastname: Schmetterer
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001783:Blood Flow Velocity; D002829:Choroid / Q000098:blood supply*; D018592:Cross-Over Studies; D015237:Dinoprost / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000037:antagonists & inhibitors*; D006801:Humans; D007262:Infusions, Intravenous; D007368:Interferometry; D017078:Laser-Doppler Flowmetry; D008027:Light; D008297:Male; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D019332:Endothelin-1; C072630:isopropyl unoprostone; D015237:Dinoprost