Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl.
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.
Polska
Elzbieta
E
Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Doelemeyer
Arno
A
Luksch
Alexandra
A
Ehrlich
Paulina
P
Kaehler
Nils
N
Percicot
Christine L
CL
Lambrou
George N
GN
Schmetterer
Leopold
L
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*
D000959:Antihypertensive Agents; D019332:Endothelin-1; C072630:isopropyl unoprostone; D015237:Dinoprost