ROLE OF MAST CELL-DERIVED MEDIATORS IN ACID-INDUCED SHORTENING OF THEESOPHAGUS

It has recently been demonstrated that acid-induced esophageal mucosal injury leads to esophageal shortening, raising the possibility that r eflux esophagitis per se may contribute to the development of hiatal h ernia. The aim of the present study was to determine whether mast cell -derived mediators are involved in this acid-induced esophageal shorte ning. Changes in esophageal length were continuously monitored in anes thetized opossums while the esophageal lumen was perfused with 100 mmo l/l HCl or normal saline. Changes in esophageal length were compared b etween animals perfused with acid, with or without pretreatment with t he mast cell stabilizers doxantrazole or disodium cromoglycate (DSCG), and animals perfused with normal saline, with or without pretreatment with DSCG. In separate in vitro studies the effect of the mast cell s tabilizers on electrical field stimulation-induced esophageal longitud inal muscle contraction was determined. Gradual esophageal lengthening occurred during saline perfusion, irrespective of whether animals wer e pretreated with DSCG. In contrast, acid perfusion induced esophageal shortening, which was abolished by pretreatment with either doxantraz ole or DSCG in doses sufficient to attenuate the acid-induced mucosal histamine release. In vitro, the mast cell stabilizers had no effect o n electrical field stimulation-induced esophageal shortening. This stu dy suggests that esophageal shortening associated with acute acid-indu ced esophageal mucosal injury in the opossum is dependent on mast cell -derived mediators.