Effect of sodium-potassium pump inhibition by ouabain on the permeability of isolated visceral sheep peritoneum.

The permeability for small solutes and the ultrafiltration capacity of the peritoneum are essential for effective peritoneal dialysis (PD) treatment. Elucidation of the factors that regulate these two properties is therefore of great importance. Ouabain, a potent inhibitor of the Na+-K+ pump has been shown to reduce fluid absorption in animal models of PD. In the present study, we used Ussing chamber experiments to investigate the effect of ouabain on the transmesothelial electrical resistance (RTM) of isolated visceral sheep peritoneum. Peritoneal samples from the omentum of adult sheep were isolated immediately after the deaths of the animals and were transferred to the laboratory in cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A planar sheet of visceral peritoneum was mounted in an Ussing-type chamber, and ouabain (10(-3) mol/L) was added apically and basolaterally. The RTM was measured before and serially for 30 minutes after the addition of ouabain. Because active ion transport is temperature-dependent, all measurements were taken at 37 degrees C. The results presented are the mean +/- standard error of 6 experiments. Before the addition of ouabain, the control RTM was measured as 21.26 +/- 0.57 Omega x cm2. Addition of ouabain basolaterally induced an increase in the RTM to 27.62 +/- 0.72 Omega x cm2 within 1 minute (p < 0.05), and this level persisted throughout the experiment. The effect of ouabain, when added apically, was similar, characterized by a rapid rise in the RTM to 24.66 +/- 0. 76 Omega x cm2 at 1 minute (p < 0. 05), with subsequent persistence at that level. A clear association between RTM and active ion transport has been shown in previous studies. The results of the present study, showing a rapid effect of ouabain on the RTM of visceral peritoneum, therefore clearly suggest that cell membrane Na+K+-ATPase is important for peritoneal ionic transport. In addition, ouabain was previously shown to reduce vasodilation and intraperitoneal sodium or to increase intraperitoneal volume, especially in the presence of conventional acidic solutions. Those findings, combined with the results of the present study, clearly indicate that intraperitoneal administration of digitalis glycosides may have some beneficial effect in PD patients; however the specific clinical implications need further investigation.