Effect of hyperosmolality upon the mesothelial monolayer exposed in vivo and in situ to a mannitol-enriched dialysis solution

Studies done using the in vivo mouse model of population analysis of mesoth elium showed that dialysis solutions containing high concentrations of gluc ose induced the development of a hypertrophic phenotype. Since these change s were neither related to the low pH nor to the presence of lactate buffer, we hypothesized that the presence of glucose was at the origin of the obse rved alterations. Theoretical analysis of the problem points to three possi ble mechanisms: hyperosmolality; metabolic changes derived from the high-gl ucose concentration itself, and/or the presence of products derived from th e nonenzymatic degradation of glucose. The present study was designed to de monstrate or rule out the eventual effect of hyperosmolality upon the monol ayer, applying the in vivo mouse model of population analysis of mesotheliu m. For this purpose, morphometric observations made in mice injected once a day during 30 consecutive days with a filter-sterilized 4.25% solution of mannitol (233.29 mM) were compared with those seen in intact mice and in a previously reported group of animals exposed to heat-sterilized fluid, havi ng an equimolar concentration of glucose (235.9 mM), and the same osmolalit y (486 mosm/l) and electrolyte concentrations. The main findings observed i n the mannitol-treated mice during the period of exposure included increase d cell size and cytoplasmic surface area, as well as decreased cell viabili ty. The regenerative capabilities of the exposed mesothelium remained intac t. After a recovery period of 7 days, the aforementioned parameters reverte d to normal values. This pattern is significantly different from the hypert rophic, senescent and low regenerative phenotype observed in mice treated w ith the high-glucose concentration solution. We conclude that, at least in the in vivo and in situ setup, the detrimental effects of hyperosmolality a lone upon the exposed mesothelium are quite limited and fully reversible wi thin a recovery period of 7 days.