EFFECTS OF ENDOTHELIN-1 (ET-1) ON OCULAR HEMODYNAMICS

Purpose. There is evidence from in vitro and animal data that endothel in-1 (ET-1) plays an important role in ocular blood flow. The aim of t he present study was to investigate the effect of systemic ET-1 admini stration on ocular circulation in healthy subjects. Methods. In a doub le 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 we ll as ocular fundus pulsations in the macula and the optic disc, and s ystemic hemodynamic parameters were measured. Results. ET-1 dose-depen dently reduced fundus pulsations in the macula (maximum effect -12 +/- 2% versus baseline; p < 0.001 versus baseline and placebo) and the op tic 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 dose s which do not affect systemic hemodynamics or flow velocity in the op hthalmic artery. These results indicate that ocular circulation is par ticularly sensitive to changes in local ET-1 concentration and confirm s the hypothesis that ET-1 may play a role in ocular vascular diseases .