Nitrite-derived nitric oxide formation and its pathophysiological effects following ischemia-reperfusion injury in kidney

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Nitric oxide (NO) has many physiological functions, and nitric oxide synthase (NOS) makes NO by catalyzing the oxygen-, tetrahydrobiopterin-, and NADPH-dependent oxidation of L-arginine, and nitrite and nitrate are recognized as a waste forms of NO. We hypothesized that oral nitrite is decomposed to NO, and this NO is distributes to the blood and have a physiological role in vivo. In this study, we measured hemoglobin(Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy and showed nitrite-derived NO formation in renal ischemia-reperfusion injury.<Results>1.Intravenous infusion of sodium nitrite facilitated the formation of HbNO during renal ischemia, which demonstrated that the origin of NO was nitrite.2.The EPR signal of HbNO in kidney appeared after 40 min of renal ischemia, and renal reperfusion decreased the HbNO level in the kidney and increased it in blood by contrast.3.The amount of HbNO was nitrite concentration dependent, and this formation was NOS independent.4.Three weeks of of L-NAME treatment resulted in a marked rise in systolic blood pressure and co-administration of sodium nitrite (1000mg/L) lessened the L-NAME-induced hypertension (L-NAME ; 170+/-11mmHg vs L-NAME+nitrite;141+/-16mmHg). In addition, co-administration of nitrite with L-NAME attenuated L-NAME-induced renal histrogical changes.These results suggest that oral nitrite increases circulating NO and may have an important physiological role in protecting following ischemia-reperfusion injury in kidney.