Role of PGE2/EP2 Receptor Signaling on The Effects of Neonatal Hyperoxia on Airway Smooth Muscle

Abstract

It was shown that neonatal hyperoxic‐exposure associates with airway hyperresponsiveness and impaired nonadrenergic noncholinergic relaxation. It was demonstrated that reduced relaxant responses were associated with an impairment of prostaglandin E2 (PGE2) release from airway smooth muscle (ASM). In this study we tested the hypothesis that supplementation of PGE2 or EP2 agonists to ASM restore relaxant responses. Tracheal cylinders were obtained from 12 days rat pups exposed to hyperoxia or room air for seven days. These cylinders were used to study contractile and relaxant responses. In hyperoxic tracheal preparations the contractile responses to bethanechol were enhanced as compared to room air controls. These enhanced contractile responses were attenuated by pre‐incubation of tissues with PGE2 (1µM). Similar effect was showed by using an EP2 agonist. This effect of PGE2 and EP2 agonist was reversed by an EP2 antagonist. PGE2 and EP2 induced dose response relaxations of ASM, which were reduced by an EP2 antagonist.We conclude that PGE2 induces relaxation of airways via EP2 receptors, and the use of EP2 agonists may serve as a therapeutic approach to overcome the adverse effects of neonatal hyperoxia on relaxant responses of ASM.Support by MEST