Increased intragallbladder pressure stimulates gallbladder eicosanoid release.

Abstract

The stimulus for increased gallbladder eicosanoid synthesis during cholecystitis is unknown. This study examines the hypothesis that increased intragallbladder pressure stimulates endogenous gallbladder eicosanoid release. Rabbit gallbladders were perfused in vitro at 1 ml/minute with oxygenated Krebs-Henseleit buffer and subjected to 0, 12 or 24 mm Hg of intraluminal gallbladder pressure. Release of 6-keto-PGF1 alpha infinity PGE2 and thromboxane B2 were measured in all groups after 15 and 30 and 60 minutes of perfusion by enzyme immunoassay and gallbladders were examined histologically. Increasing intraluminal gallbladder pressure concomitantly increased gallbladder 6-keto-PGF1 alpha release 2 fold or more at all time of perfusion and altered gallbladder mucosal architecture by increasing basolateral edema in the submucosal space. Infusion of indomethacin (10 micrograms/ml in the perfusion media) decreased 6-keto-PGF1 alpha release from the in vitro perfused gallbladders subjected to 24 mm Hg by 70%. Increased gallbladder eicosanoid release during early cholecystitis may in part be related to the physical force of increased gallbladder intraluminal pressure on the gallbladder mucosa.