Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces.
BACKGROUND
In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces.


METHODS
Male Sprague-Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to (51)Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy.


RESULTS
Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8+/-7.1 pmol/cm(2) vs 5.8+/-2.1 pmol/cm(2)) (p<0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin).


CONCLUSIONS
Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.
Farré
Ricard
R
Center for Gastroenterological Research, Catholic University Leuven, Belgium.
De Vos
Rita
R
Geboes
Karel
K
Verbecke
Kristine
K
Vanden Berghe
Pieter
P
Depoortere
Inge
I
Blondeau
Kathleen
K
Tack
Jan
J
Sifrim
Daniel
D
D000818:Animals; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005110:Extracellular Space / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000166:cytology; D008854:Microscopy, Electron / Q000379:methods; D023421:Models, Animal; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010434:Pepsin A / Q000494:pharmacology; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism*
D005765:Gastrointestinal Agents; D010434:Pepsin A; D006851:Hydrochloric Acid