Effect of dual endothelin receptor blockade on ocular blood flow in patients with glaucoma and healthy subjects.
OBJECTIVE
Several lines of evidence indicate that altered blood flow regulation may contribute to the pathogenesis of glaucomatous optic neuropathy. Recent data support the hypothesis that the endothelin system is involved in the processes that lead to vascular dysregulation in glaucoma. This study was conducted to test the hypothesis that bosentan, a dual endothelin receptor antagonist, increases ocular blood flow in patients with glaucoma.


METHODS
Fourteen patients with primary open-angle glaucoma and 14 sex- and age-matched healthy volunteers were included. Both groups received bosentan 500 mg daily for 8 days. Ocular hemodynamics were assessed at baseline and on the last study day. Retinal vessel diameters and retinal red blood cell velocity were recorded with a retinal vessel analyser and laser Doppler velocimetry, respectively. Choroidal and optic nerve head blood flow were measured with laser Doppler flowmetry.


RESULTS
Retinal arteries and veins showed a significant dilatation after administration of bosentan in both groups (+5%-8%). Retinal blood velocity and retinal blood flow increased up to +45% after administration of bosentan in both patients and healthy subjects. Administration of bosentan increased choroidal (+12%-17%) and optic nerve head blood flow (+11%-24%) in both groups. The effect of bosentan on ocular blood flow parameters was comparable between the two groups.


CONCLUSIONS
The data from the present study indicate that dual inhibition of endothelin receptors increases ocular blood flow in patients with glaucoma and healthy subjects. Further studies are needed to study the dose-response relationship of this effect and to characterize the role of endothelin receptor subtypes.
Resch
Hemma
H
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Karl
Katharina
K
Weigert
Günther
G
Wolzt
Michael
M
Hommer
Anton
A
Schmetterer
Leopold
L
Garhöfer
Gerhard
G
D000284:Administration, Oral; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001783:Blood Flow Velocity / Q000502:physiology; D000077300:Bosentan; D002829:Choroid / Q000098:blood supply; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D005902:Glaucoma, Open-Angle / Q000503:physiopathology*; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009898:Optic Disk / Q000098:blood supply; D012039:Regional Blood Flow / Q000502:physiology; D012171:Retinal Vessels / Q000503:physiopathology*; D013449:Sulfonamides / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan