Physiological and pathophysiological role of nitrite-derived nitric oxide formation

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1. Effect of orally administered nitrite on circulating nitric oxide(NO).When 1 mg/kg Na^<15>NO_2 was orally administered to rats, marked Hb^<15>NO-derived doublet electron paramagnetic resonance (EPR) signals were observed in the blood, which indicated that orally administered nitrite can be a source of circulating NO as a form of HbNO. Co-administration of nitrite (100 mg/liter drinking water) with L-NAME (1 g/liter) for three weeks significantly attenuated the L-NAME-induced hypertension (149 ± 10 mmHg) compared to L-NAME alone (170 ± 13 mmHg). Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo.2. Nitrite-derived NO formation following ischemia-reperfusion injury in kidneyIntravenous infusion of a stable isotope of [^<15>N] nitrite facilitated the formation of Hb^<15>NO during renal ischemia, which demonstrated that the origin of NO was nitrite. Our findings suggest that nitrite can be an alternative source of NO in ischemic kidney and that it bind with hemoglobin and then spread by the circulation after reperfusion.3. Dietary dose of nitrite-derived nitric oxide improves renal injury in L-NAME-induced hypertensive ratsChronic administration of dietary dose of nitrite (1mg/L) attenuated L-NAME-induced renal histrogical changes and proteinuria. High dose of nitrite (10mg/L) also attenuated L-NAME-induced renal injury. We conclude that dietary nitrite-derived NO generation system may serve as a backup system for NO generation when the NOS/L-arginine-dependent NO generation system is compromised. Our findings may explain, at least in part, the mechanism of the vegetables and fruit rich diet-induced prevention of cardiovascular disease.