Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina

PURPOSE. There is evidence that ocular bloodflow strongly depends on arteri al oxygen tension. Results from recent animal studies indicate that the vas oconstrictor response to hyperoxia may be mediated in part by an increased production of endothelin (ET)-1. In an effort to answer the question whethe r the retinal vasoconstrictive response to hyperoxia in humans is mediated through ET-1, changes in ocular hemodynamics induced by 100% O-2 breathing were studied in the absence and presence of an ETA receptor antagonist (BQ- 123). METHODS, The study was a randomized, placebo-controlled double-masked, bala nced, three-way crossover design. On separate study days 15 healthy male su bjects received infusions of BQ-123 (either 60 mu g/min or 120 mu g/min) or placebo. The effects of BQ-123 or placebo on hyperoxia-induced (100% O-2 b reathing) changes in retinal and pulsatile choroidal blood how were assesse d with the blue-field entoptic technique and with laser interferometric mea surement 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 puls ation amplitude between -7% and -8% (P < 0.001). BQ-123 dose dependently bl unted the response to hyperoxia in the retina (60 mu g/min: -25%, 120 mu g/ min: -20%; P = 0.003), but not in the choroid. CONCLUSIONS. These results indicate that ET-1 contributes to hyperoxia-indu ced retinal vasoconstriction in the human retina.