The effects of ETB receptor-selective agonist on IOP and blood-aqueous barrier in rabbit eyes: role of cyclooxygenase products.

The authors have reported that ET-1 and ETB receptor agonist, sarafotoxin S6c (STX-S6c), caused prolonged intraocular pressure (IOP) reduction in rabbit eyes in a dose-dependent fashion when injected intravitreally. The purpose of this study was to determine the effects of STX-S6c on the blood-aqueous barrier and also the possible role of cyclooxygenase products in modulating IOP. Indomethacin, a cyclooxygenase inhibitor (50 mg/kg), or its placebo was administered intraperitoneally 1 hour before or 1 hour before and 4 hours after the intravitreal injection of 0.5 micrograms of STX-S6c into one eye in a group of albino rabbits. The fellow eye received the vehicle only. IOP was measured prior to and periodically up to 120 hours after the injection using a calibrated pneumatonometer. One hour and 24 hours following the injection of STX-S6c (0.5 micrograms) with or without indomethacin, approximately 100 microL of aqueous humor was withdrawn by paracentesis. Protein concentration was measured by Lowry's method and PGE2 concentration was determined by radioimmunoassay. Both single and double dosings of indomethacin failed to prevent the IOP reduction caused by STX-S6c. The eyes injected with STX-S6c exhibited a significant elevation of both PGE2 and protein concentration at both 1 and 24 hours after injection. Pretreatment with indomethacin could significantly suppress the PGE2 and protein content of aqueous humor at both 1 and 24 hours after injection. ETB receptor agonist, STX-S6c, appears to induce the IOP reduction without affecting the cyclooxygenase pathway or disrupting the blood-aqueous barrier.