Effects of Endothelin Receptor Antagonists on Anterior Chamber Inflammation Induced by Intravitreal Injection of Endothelin-1

Abstract

To investigate the role of endothelin receptors (ETAand ETB) in the inflammatory reaction induced by endothelin-1 (ET-1), the time course of changes in aqueous protein concentration (APC) after the intravitreal injection of ET-1 (10−4, 10−5m) was measured using a laser flare-cell meter in pigmented rabbit eyes. The effects of pre-treatment with specific ETAreceptor antagonist (97-139) (10−1, 10−2, 10−3, 10−4m), specific ETBreceptor antagonist (BQ-788) (1.6×10−3m), and vehicle solution were assessed. The influence of ETAreceptor antagonist pre-treatment on aqueous prostaglandin E2and leukotriene B4concentrations was also evaluated. As a result, pre-treatment with ETAreceptor antagonist blocked the APC increase induced by 10−4m ET-1 in a dose dependent fashion, while BQ-788 did not suppress the inflammatory reaction. The injection of ET-1 increased aqueous prostaglandin E2concentration, which was inhibited by pre-treatment with ETAreceptor antagonist. Aqueous leukotriene B4concentration was not affected by ET-1 nor ETAreceptor antagonist. In conclusion, ETAreceptor mediates the increases in aqueous protein and prostaglandin E2concentration induced by ET-1 injection, and this inflammatory reaction occurs via the cyclooxygenase pathway of arachidonic acid cascade.