Urinary nitrite: More than a marker of infection

The bacteriostatic gas nitric oxide (NO) is formed when nitrite is acidified. Infected urine may contain considerable amounts of nitrite as a result of bacterial nitrate reductase activity, and detection of nitrite in urine is routinely used in the diagnosis of bacterial cystitis. We sought to determine whether NO was generated from acidified nitrite-containing urine. Furthermore, we also studied the growth of the urinary pathogen Escherichia coli in acidified nitrite-containing urine. Urine, collected from healthy control subjects or from patients with infected nitrite-containing urine, was acidified and incubated in a closed syringe with varying amounts of nitrite added. After 30 minutes, the headspace gas was removed and immediately injected into a chemiluminescence NO analyzer. In addition, NO was measured in urine collected from healthy control subjects after ingestion of vitamin C. Bacterial growth was measured continuously in control urine for 10 hours after incubation for 2 hours in acidic urine with varying concentrations of nitrite added. Large amounts of NO were released from infected nitrite-containing urine after mild acidification. NO was also released from acidified control urine if nitrite was added, and this release was greatly potentiated in the presence of vitamin C. Furthermore, the growth of E. coli was markedly reduced by the addition of nitrite to acidified urine. We propose that nitrite-producing bacteria induce their own death in acidic urine by supplying substrate for generation of bacteriostatic compounds such as NO. This mechanism might explain why urinary acidification and vitamin C may be effective in the treatment of bacteriuria.