Urinary nitrite: more than a marker of infection
Abstract
Objectives 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 coll in acidified nitrite-containing urine.Methods 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.Results 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.Conclusions 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.
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Cites
Nitric oxide: physiology, pathophysiology, and pharmacology.
Moncada, S., Palmer, R. M., & Higgs, E. A. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06663-3 · Cited by 15,525 · see citing works
Benjamin, N., O'Driscoll, F., Dougall, H., Duncan, C., Smith, L., Golden, M., & McKenzie, H. (1994) · Nature · doi:10.1038/368502a0 · Cited by 665 · see citing works
Intragastric nitric oxide production in humans: measurements in expelled air.
Lundberg, J. O., Weitzberg, E., Lundberg, J. M., & Alving, K. (1994) · Gut · doi:10.1136/gut.35.11.1543 · Cited by 661 · see citing works
Self-citationInhibitors of endogenous nitrosation mechanisms and implications in human cancer prevention
Bartsch, H., Ohshima, H., & Pignatelli, B. (1988) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/0027-5107(88)90194-7 · Cited by 296 · see citing works
Dykhuizen, R. S., Frazer, R., Duncan, C., Smith, C. C., Golden, M., Benjamin, N., & Leifert, C. (1996) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.40.6.1422 · Cited by 239 · see citing works
Effect of nitric oxide on staphylococcal killing and interactive effect with superoxide
Kaplan, S. S., Lancaster, J. R., BASFORD, R. E., & Simmons, R. L. (1996) · Infection and Immunity · doi:10.1128/iai.64.1.69-76.1996 · Cited by 119 · see citing works
Kono, Y., Shibata, H., Adachi, K., et al. (1994) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1994.1220 · Cited by 59 · see citing works
Bacteriostatic Action of Nitrates
Tarr, H. L. A. (1941) · Nature · doi:10.1038/147417b0 · Cited by 54 · see citing works
Brandt, R., Guyer, K. E., & Banks, W. L. (1977) · American Journal of Clinical Pathology · doi:10.1093/ajcp/68.5.592 · Cited by 15 · see citing works
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The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · see citing works
Self-citationMethods to detect nitric oxide and its metabolites in biological samples
Bryan, N. S., & Grisham, M. B. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.04.026 · Cited by 1,005 · see citing works
Nitrate, bacteria and human health
Lundberg, J. O., Weitzberg, E., Cole, J. A., & Benjamin, N. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro929 · Cited by 739 · see citing works
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van Faassen, E. E., Bahrami, S., Feelisch, M., Hogg, N., Kelm, M., Kim‐Shapiro, D. B., Kozlov, A. V., Li, H., Lundberg, J. O., Mason, R., et al. (2009) · Medicinal Research Reviews · doi:10.1002/med.20151 · Cited by 435 · see citing works
Self-citationMaia, L. B., & Moura, J. J. G. (2014) · Chemical Reviews · doi:10.1021/cr400518y · Cited by 401 · see citing works
NO Generation From Nitrite and Its Role in Vascular Control
Lundberg, J. O., & Weitzberg, E. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000161048.72004.c2 · Cited by 341 · see citing works
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Modin, A., Björne, H., Herulf, M., Alving, K., Weitzberg, E., & Lundberg, J. O. N. (2001) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2001.00771.x · Cited by 346 · see citing works
Self-citationNonenzymatic Nitric Oxide Production in Humans
Weitzberg, E., & Lundberg, J. O. N. (1998) · Nitric Oxide · doi:10.1006/niox.1997.0162 · Cited by 296 · see citing works
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Bryan, N. S. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.019 · Cited by 260 · see citing works
Carlsson, S., Wiklund, N. P., Engstrand, L., Weitzberg, E., & Lundberg, J. O. N. (2001) · Nitric Oxide · doi:10.1006/niox.2001.0371 · Cited by 189 · see citing works
Self-citationRed wine-dependent reduction of nitrite to nitric oxide in the stomach
Gago, B., Lundberg, J. O., Barbosa, R. M., & Laranjinha, J. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.06.007 · Cited by 186 · see citing works
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Weitzberg, E., Hezel, M., Lundberg, J. O., & Warner, D. S. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181fcf3cc · Cited by 145 · see citing works
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Gautier, C., van Faassen, E., Mikula, I., Martasek, P., & Slama-Schwok, A. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.031 · Cited by 143 · see citing works
Nitrite is an alternative source of NO in vivo
Tsuchiya, K., Kanematsu, Y., Yoshizumi, M., Ohnishi, H., Kirima, K., Izawa, Y., Shikishima, M., Ishida, T., Kondo, S., Kagami, S., et al. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00525.2004 · Cited by 127 · see citing works
Inorganic nitrite therapy: historical perspective and future directions
Kevil, C. G., Kolluru, G. K., Pattillo, C. B., & Giordano, T. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.042 · Cited by 113 · see citing works
Gago, B., Nyström, T., Cavaleiro, C., Rocha, B. S., Barbosa, R. M., Laranjinha, J., & Lundberg, J. O. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.04.027 · Cited by 48 · see citing works
Self-citationTsuchiya, K., Takiguchi, Y., Okamoto, M., Izawa, Y., Kanematsu, Y., Yoshizumi, M., & Tamaki, T. (2004) · Journal of Pharmacological Sciences · doi:10.1254/jphs.fmj04006x3 · Cited by 29 · see citing works
- Authors
- Lundberg, J. O. N., Carlsson, S., Engstrand, L., Morcos, E., Wiklund, N. P., & Weitzberg, E.
- Affiliations
- Karolinska University Hospital (SE)
- Corresponding author
- Lundberg, J.O.N.
- Venue
- Urology
- Publisher
- Elsevier BV
- Published
- 1997-08
- Volume
- 50
- Issue
- 2
- Pages
- 189-191
- ISSN
- 0090-4295 (ISSN-L)
- OpenAlex
- W2079331192
- Cited by
- 108
- References
- 9
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 8 · 2018: 2 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 4
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Urology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Urinary Tract Infections Management
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Kidney Stones and Urolithiasis Treatments
- Keywords
- urinary nitrite, nitric oxide, bacterial cystitis, Escherichia coli, bacterial growth inhibition, urinary acidification, vitamin C, nitrate reductase
- MeSH terms
- Escherichia coli, Humans, Hydrogen-Ion Concentration, Nitric Oxide, Nitrites, Urinary Tract Infections, Urine
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