Effects of washout following indomethacin administration on electrical field stimulation–induced isolated rat gastric fundus strip contractions

Abstract

Although gastric hypermotility is one of the mechanisms proposed to explain the ulcerogenic action of indomethacin, the drug has shown relaxatory effects on isolated longitudinal and transverse rat gastric fundus. To explain the above discrepancy, the aim of this study was to investigate the effects of washout following indomethacin administration on the contractile response of isolated rat gastric strips to electrical field stimulation. Transverse and longitudinal strips of stomach were suspended in organ baths containing oxygenated Krebs solution. Contractile responses to electrical field stimulation were recorded on a physiograph before and after administration of a single concentration of indomethacin. Recordings were also taken 15 min after the washout of the drug. To study the part played by K(ATP) channels on post-washout response, the effects of diazoxide as a channel opener and glybenclamide as a channel blocker were also studied. The amplitude of the contractions was not changed following indomethacin administration but was significantly increased 15 min after washout of the drug. Diazoxide pretreatment inhibited the stimulatory post-washout response of both strips. Glybenclamide pretreatment showed different results depending on the type of strip. In the transverse strips the drug showed no effect while in the longitudinal strips it decreased the post-washout response. The present data suggest that indomethacin has a delayed stimulatory effect on gastric smooth muscle, which will appear after the exposure of the strip to the drug followed by its washout. This effect seems to be under the influence of K(ATP) channel modulators.