Alterations in rat jejunal permeability to a macromolecular tracer during a hyperosmotic load

The effects of intraluminal hyperosmolality on the intestinal permeability of a macromolecular tracer, horseradish peroxidase, was assessed in rats by light and electron microscopic cytochemistry. After 60 minutes of an intraluminal hypertonic perfusion of 600 mOsM mannitol, horseradish peroxidase was demonstrable in the intercellular spaces between adjacent absorptive epithelial cells of jejunal villi, along the microvillar brush border, in numerous pinocytotic vesicles, in multivesicular bodies, as well as in large lysosomes. Horseradish peroxidase was frequently found extending from the luminal surface of the cell through the tight junctional region and into more basal portions of the intercellular space. In occasional cells, fragments of the interdigitating plasma membranes of two adjacent absorptive cells appeared to bud off into the cytoplasm of one cell. In contrast, after 60 minutes of isotonic perfusion, horseradish peroxidase was confined to the microvillar brush border, a few pinocytotic vesicles, and occasional multivesicular bodies. These experiments suggest that the passage of macromolecules across the jejunal epithelium of adult rats is enhanced under conditions of luminal hyperosmotic stress. This may be due to an alteration in the functional integrity of the tight junctional macromolecular barrier or to an enhanced rate of pinocytosis.