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Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces
  1. Ricard Farre (ricard.farremarti{at}med.kuleuven.be)
  1. Catholic University Leuven, Belgium
    1. Rita De Vos (rita.devos{at}med.kuleuven.be)
    1. Catholic University Leuven, Belgium
      1. Karel Geboes (karel.geboes{at}uz.kuleuven.ac.be)
      1. Catholic University Leuven, Belgium
        1. Kristin Verbeke (kristin.verbeke{at}pharm.kuleuven.be)
        1. Catholic University Leuven, Belgium
          1. Pieter Vanden Berghe (pieter.vandenberghe{at}med.kuleuven.be)
          1. Catholic University Leuven, Belgium
            1. Inge Depoortere (inge.depoortere{at}med.kuleuven.be)
            1. Catholic University Leuven, Belgium
              1. Kathleen Blondeau (kathleen.blondeau{at}med.kuleuven.be)
              1. Catholic University Leuven, Belgium
                1. Jan Tack (jan.tack{at}med.kuleuven.be)
                1. Catholic University Leuven, Belgium
                  1. Daniel Sifrim (daniel.sifrim{at}med.kuleuven.be)
                  1. Catholic University Leuven, Belgium

                    Abstract

                    Background: In patients with non-erosive GERD, heartburn can occur when acid reaches sensory nerve endings through oesophageal mucosa dilated intercellular spaces. Life stress 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 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 51Cr-EDTA (400 daltons), FITC-dextran 4000 daltons (FD4) and FITC-dextran 20000 daltons (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0 + pepsin 1 mg/mL. 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/cm2 vs. 5.8 ± 2.1 pmol/cm2) (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.

                    • dilated intercellular spaces
                    • oesophageal mucosa
                    • permeability
                    • rat
                    • stress

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