Comparative study of the effect of luminal hypotonicity on mucosal permeability in rat upper gastrointestinal tract.
OBJECTIVE
To investigate whether the increase in mucosal permeability in the duodenum, induced by luminal hypotonicity, also occurs in the stomach and the jejunum and whether this increase in permeability can be explained by epithelial injury.


METHODS
The stomach, duodenum or jejunum of the anaesthetized rat were perfused with a hypotonic solution and effects on mucosal permeability (blood-to-lumen clearance of radioactive probes); luminal alkalinization and net fluid flux were determined in the absence and presence of cyclooxygenase inhibition.


RESULTS
The hypotonicity-induced (50 mM NaCl) increase in duodenal mucosal permeability was markedly larger in cyclooxygenase-2-inhibited animals than in controls and associated with a 20% decrease in luminal alkalinization and increased fluid absorption. Perfusion with 50 mM NaCl increased duodenal mucosal permeability to all probes investigated, i.e. (14)C-urea, (14)C-methyl-D-glucose, (51)Cr-EDTA and (14)C-inulin. The percentage increase in permeability was the greatest for inulin and the lowest for urea. Luminal hypotonicity caused superficial villous tip damage in some but not in all duodenal specimens but there was no difference in morphology between controls and cyclooxygenase-2-inhibited animals. Jejunum, but not the stomach, responded to luminal hypotonicity by increasing net fluid absorption, mucosal permeability (greater than sixfold) and the rate of luminal alkalinization (>100%).


CONCLUSIONS
The stomach does not respond while the jejunum is more sensitive to hypotonicity-induced increase in mucosal permeability than the duodenum. The hypotonicity-induced increase in duodenal mucosal permeability most probably constitutes a physiological mechanism that entails widening of paracellular pathways, which facilitates the transport of osmolytes into the lumen.
Pihl
L
L
Department of Neuroscience, Division of Physiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Wilander
E
E
Nylander
O
O
D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007038:Hypotonic Solutions / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007444:Inulin / Q000493:pharmacokinetics; D007555:Isoxazoles / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008757:Methylglucosides / Q000493:pharmacokinetics; D009994:Osmolar Concentration; D010539:Permeability / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects; D041742:Upper Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism; D014508:Urea / Q000493:pharmacokinetics
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007038:Hypotonic Solutions; D007555:Isoxazoles; D008757:Methylglucosides; D012965:Sodium Chloride; C027020:methylglucoside; D014508:Urea; D007444:Inulin; C409945:parecoxib; D007213:Indomethacin