Effects of BQ-123, an ETA recepter-selective antagonist, on changes of intraocular pressure, blood-aqueous barrier and aqueous prostaglandin concentrations caused by endothelin-1 in rabbit

Abstract

Endothelin-1 (ET-1) is known to affect the intraocular pressure (IOP) in rabbits. We reported that intravitreally administered ET-1 induced biphasic IOP response, an early transient IOP rise followed by a subsequent prolonged decrease. In an attempt to clarify the role of ET receptor subtypes in the IOP responses following ET-1 injection, we studied the effects of ETA receptor-specific antagonist, BQ-123, in rabbits. We also evaluated the possible role of prostaglandins (PGs) and the disruption of the blood-aqueous barrier (BAB) following ET-1 injection in modulating the IOP change. BQ-123 (126.5 or 12.6 micrograms) was injected into the vitreous (20 microL/eye) of one eye in a group of 5 rabbits. Contralateral eyes received the same amount of vehicle in a masked randomized fashion. The same amount of ET-1 (0.5 or 0.05 micrograms) was injected intravitreally 30 minutes later into both eyes. IOP was measured prior to and periodically up to 120 hours after injection using a calibrated pneumatonometer. In another experiment BQ-123 (126.5 micrograms) was injected into one eye of 4 rabbits and the other eye served as a control to observe the effect of BQ-123 on the IOP. One hour and 24 hours following the injection of BQ-123 and ET-1, approximately 100 microL of aqueous humor was withdrawn by paracentesis. Protein concentration was measured by Lowry's method and PGE2 concentration, by radioimmunoassay. BQ-123 had no effect on the IOP when used alone. When used in combination with ET-1, BQ-123 (126.5 micrograms) significantly inhibited both the IOP rise (0.5-1 hour) and the reduction (24-72 hours) caused by ET-1 (0.5 microgram). BQ-123 (12.6 micrograms) also significantly inhibited the IOP reduction (6-8 hours and 72-96 hours) caused by ET-1 (0.05 micrograms). Pre-injection of BQ-123 (126.5 micrograms) significantly suppressed the increase in the aqueous protein and the PGE2 concentration both at 1 and 24 hours. The IOP response and the elevation of aqueous protein and PGE2 concentration following ET-1 injection are at least partly mediated by ETA receptors.