Intraocular pressure response to intravitreal injection of endothelin-1 and the mediatory role of ETA receptor, ETB receptor, and cyclooxygenase products in rabbits.

Endothelin-1 (ET-1) affects intraocular pressure (IOP) in rabbits. First, we studied IOP responses to the intravitreal injection of various doses of ET-1 ranging from 5 ng to 5 micrograms in unanesthetized rabbits, and observed a transient rise in IOP, from 0.5 to 2 h in duration, invariably followed by a prolonged IOP reduction, lasting for more than 72 h in rabbits treated with 0.5 microgram and 5 micrograms of ET-1. ET-1 (0.05 microgram and 0.15 microgram) resulted in a prolonged IOP reduction without an early IOP rise. Both IOP rise and reduction were significantly related to the dose of ET-1. A masked, randomized, study revealed that the intraperitoneal administration of indomethacin (50 mg/kg) prior to ET-1 injection significantly reduced the ocular hypertensive response, but not th ocular hypotensive response, to ET-1. The ETA receptor selective antagonist, 97-139 (155 micrograms) had no effect on IOP when used alone. However, when used in combination with 0.5 microgram of ET-1, 97-139 significantly inhibited both the IOP rise (0.5-2 h) and reduction (8-96 h) caused by ET-1. The ETB receptor selective agonist, sarafotoxin S6c (0.5 microgram), caused a sustained IOP reduction of 2 to 96 h in duration without the initial IOP rise. We also determined the concentration of prostaglandin (PG) E2 in the aqueous humor using radioimmunoassay techniques on samples obtained at 1 and 24 h after ET-1 injection, and examined the effects of pretreatment with indomethacin or 97-139 on PGE2 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)