Effect of NaCl and urea concentration comparable to renal medulla on superoxide production by human polymorphonuclear...

The influence of hyperosmolarity on superoxide production by polymorphonuclear leukocytes (PMNL) was examined using NaCl and urea as osmotic substances. Superoxide production was inhibited in a hyperosmotic environment produced by high concentrations of these substances with the following IC50: 440 +/- 75 (SD) mOsm/kg for NaCl and 660 +/- 100 for urea. In the case of NaCl, this inhibition was time-dependent and abolished at 4 degrees C. Since PMNL pump out Na+ ion for maintenance of cellular volume in an energy dependent fashion, it was suggested that the inhibition of superoxide production was due to the exhaustion of energy stores. On the other hand, urea inhibition was almost immediate and remained even when preincubation was performed at 4 degrees C. Because the transport of urea through the cell membrane is known to be energy independent, these findings suggested that urea was either an inhibitor of the NADPH oxidase or a scavenger of superoxide anion.