Background: It has previously been shown that luminal hypotonicity increases duodenal mucosal permeability to 51Cr-EDTA. In this study we aimed to answer the following question: 1. Does luminal hypotonicity increase mucosal permeability also in the stomach and the jejunum? 2.Does luminal hypotonicity increase duodenal mucosal permeability to other probes as well? 3. Is the hypotonicity-induced increase in duodenal mucosal permeability associated with mucosal damage?

Methods: Experiments were performed in anesthetized rats in vivo. The stomach, duodenum or jejunum was perfused with a hypotonic solution and effects on mucosal permeability and bicarbonate secretion determined in the absence and presence of COX inhibitors. In some rats the duodenum was fixed in buffered formalin for histological analysis.

Results: Perfusion of the duodenum with 50 mM NaCl slightly increased mucosal permeability, an effect that was markedly augmented by COX-2 inhibition. Histological analysis revealed that luminal hypotonicity either had no effect or caused minor derangement of some cells in the villous tips. Jejunum, but not the stomach, responded to hypotonicity with a marked increase in mucosal permeability that was closely correlated to increases in bicarbonate secretion. Luminal hypotonicity increased duodenal mucosal permeability to 14C-urea, 14C-methyl-D-glucose and 14C-inulin. The percentage increase in permeability was greatest for inulin and lowest for urea.

Conclusions: The hypotonicity-induced increase in mucosal permeability is not unique for the duodenum but occurs also in the jejunum. The hypotonicity-induced increase in duodenal mucosal permeability is not due to mucosal injury but possibly reflects physiological dilatation of tight junctions.