Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina.
OBJECTIVE
There is evidence that ocular blood flow strongly depends on arterial oxygen tension. Results from recent animal studies indicate that the vasoconstrictor response to hyperoxia may be mediated in part by an increased production of endothelin (ET)-1. In an effort to answer the question whether the retinal vasoconstrictive response to hyperoxia in humans is mediated through ET-1, changes in ocular hemodynamics induced by 100% O2 breathing were studied in the absence and presence of an ET(A) receptor antagonist (BQ-123).


METHODS
The study was a randomized, placebo-controlled, double-masked, balanced, three-way crossover design. On separate study days 15 healthy male subjects received infusions of BQ-123 (either 60 microg/min or 120 microg/min) or placebo. The effects of BQ-123 or placebo on hyperoxia-induced (100% O2 breathing) changes in retinal and pulsatile choroidal blood flow were assessed with the blue-field entoptic technique and with laser interferometric measurement of fundus pulsation, respectively.


RESULTS
During baseline conditions, hyperoxia caused a decrease in retinal blood flow between -29% and -34% (P<0.001) and a decrease in fundus pulsation amplitude between -7% and -8% (P<0.001). BQ-123 dose dependently blunted the response to hyperoxia in the retina (60 microg/min: -25%, 120 microg/min: -20%; P = 0.003), but not in the choroid.


CONCLUSIONS
These results indicate that ET-1 contributes to hyperoxia-induced retinal vasoconstriction in the human retina.
Dallinger
S
S
Department of Clinical Pharmacology, Vienna University, Austria.
Dorner
G T
GT
Wenzel
R
R
Graselli
U
U
Findl
O
O
Eichler
H G
HG
Wolzt
M
M
Schmetterer
L
L
D000328:Adult; D001775:Blood Circulation / Q000502:physiology; D001783:Blood Flow Velocity; D002829:Choroid / Q000098:blood supply*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D007962:Leukocytes / Q000502:physiology; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D012171:Retinal Vessels / Q000502:physiology*; D014661:Vasoconstriction; D014788:Vision, Entoptic
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)