HCl-induced cell edema in rabbit esophageal epithelium: a bumetanide-sensitive process.
OBJECTIVE
The morphology of acid damage to esophageal epithelium is characterized by marked cell (swelling) edema. This observation suggests that, in the process of acid damage, an increase in osmotic forces develops within the cell that accounts for the increase in cell water. The aim of this study was to document that esophageal cells swell at acidic pH and to explore the nature of the osmolytes and mechanisms responsible for it.


METHODS
Cell edema was assessed in sections of rabbit esophageal epithelium by correlating morphological change with change in tissue wet weight after immersion in acidic solutions for up to 4 hours.


RESULTS
At pH < or = 2 for 2 hours, tissues gained weight and showed cell edema on both light and electron microscopy. In addition to being time- and pH-dependent, cell edema was dependent on bathing solution osmolytes, specifically Na+, K+, and Cl-, and could be inhibited by tissue pretreatment with bumetanide (or ethacrynic acid).


CONCLUSIONS
HCl exposure can spontaneously produce cell edema in esophageal epithelium. The phenomenon is pH- and time-dependent and requires acid stimulation of osmolyte absorption through a bumetanide-sensitive process compatible with an NaK2Cl cotransporter in the epithelial cell membrane.
Tobey
N A
NA
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Cragoe
E J
EJ
Orlando
R C
RC
D000818:Animals; D001834:Body Water / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D006851:Hydrochloric Acid / Q000494:pharmacology*; D017136:Ion Transport; D009995:Osmosis / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D014018:Tissue Distribution
D002712:Chlorides; D002034:Bumetanide; D012964:Sodium; D006851:Hydrochloric Acid; D011188:Potassium