[The effect of an endothelin receptor antagonist, 97-139, on intraocular pressure in rabbits]

We studied intraocular pressure (IOP) response to an intravitreal injection of 10(-5)M (20 microliters) endothelin-1 (ET-1) in unanesthetized rabbits, and found a transient IOP rise followed by a prolonged IOP reduction. ET-1 (10(-6)M) caused a sustained IOP reduction without an initial IOP rise. The ETA receptor selective antagonist, 97-139 (10(-2)M, 20 microliters), had no effect when used alone; however, when used in combination with ET-1 (10(-5)M), 97-139 (10(-2)M) significantly blocked the ocular hypotensive response to ET-1. 97-139 (10(-3)M), when used with 10(-6)M ET-1, also suppressed the IOP reduction induced by ET-1. Aqueous prostaglandin (PG) E2, determined by radioimmunoassay, was significantly elevated following intravitreal injection of ET-1 (10(-5)M). Prior injection of 97-139 (10(-2)M) significantly suppressed the elevation of aqueous PGE2 concentration caused by ET-1 (10(-5)M). These results suggest that both the IOP response and the elevation of aqueous PGE2 following ET-1 injection are at least partially mediated by ETA receptor.