Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in kidney

Nitric oxide (NO) is synthesized from l-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are believed to be waste forms of NO. We previously reported an enzyme-independent pathway of NO generation from nitrite in acidic conditions. In this study, we show nitrite-derived NO formation...

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Bibliographic Details
Published in:American journal of physiology. Renal physiology 2005-01, Vol.288 (1), p.F182-F187
Main Authors: Okamoto, Masumi, Tsuchiya, Koichiro, Kanematsu, Yasuhisa, Izawa, Yuki, Yoshizumi, Masanori, Kagawa, Susumu, Tamaki, Toshiaki
Format: Article
Language:English
Subjects:
Animals
Electron Spin Resonance Spectroscopy
Hemoglobins - metabolism
Kidney - metabolism
Male
Nitric Oxide - biosynthesis
Nitric Oxide Synthase - metabolism
Nitrites - metabolism
Rats
Rats, Sprague-Dawley
Reperfusion Injury - metabolism
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Summary:Nitric oxide (NO) is synthesized from l-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are believed to be waste forms of NO. We previously reported an enzyme-independent pathway of NO generation from nitrite in acidic conditions. In this study, we show nitrite-derived NO formation in renal ischemia-reperfusion injury using electron paramagnetic resonance (EPR) spectroscopy. In this experiment, we utilized a stable isotope of [(15)N]nitrite as a source of nitrite to distinguish l-arginine-derived NO from [(15)N]nitrite-derived (15)NO. Intravenous infusion of a stable isotope of [(15)N]nitrite ((15)NO(2)(-)) facilitated the formation of Hb(15)NO during renal ischemia, which demonstrated that the origin of NO was nitrite. The EPR signal of Hb(15)NO in kidney appeared after 40 min of renal ischemia, and renal reperfusion decreased the Hb(15)NO level in the kidney and increased it in blood by contrast. In addition, the amount of HbNO was nitrite concentration dependent, and this formation was NOS independent. Our findings suggest that nitrite can be an alternative source of NO in ischemic kidney and that it binds with hemoglobin and then is spread by the circulation after reperfusion.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00036.2004