Effects of endothelin-1 (ET-1) on ocular hemodynamics

Purpose. There is evidence from in vitro and animal data that endothelin-1 (ET-1) plays an important role in ocular blood flow. The aim of the present study was to investigate the effect of systemic ET-1 administration on ocular circulation in healthy subjects. Methods. In a double blind, placebo-controlled, randomized, 2-way cross over study in 10 healthy male subjects, we administered stepwise, increasing doses of ET-1 (0 (saline), 1.25, 2.5 and 5.0 ng/kg/minutes; 20 minutes per dose level) or placebo. Blood flow velocity in the ophthalmic artery as well as ocular fundus pulsations in the macula and the optic disc, and systemic hemodynamic parameters were measured. Results. ET-1 dose-dependently reduced fundus pulsations in the macula (maximum effect -12 ± 2% versus baseline; p < 0.001 versus baseline and placebo) and the optic disc (maximum effect: -19 ± 5% versus baseline; p < 0.001 versus baseline and placebo), but did not affect blood flow velocity in the ophthalmic artery or systemic hemodynamics. Conclusions. Endothelin-1 reduces pulsatile blood flow in the choroid and the optic disc at doses which do not affect systemic hemodynamics or flow velocity in the ophthalmic artery. These results indicate that ocular circulation is particularly sensitive to changes in local ET-1 concentration and confirms the hypothesis that ET-1 may play a role in ocular vascular diseases.