Physiological and pathophysiological role of nitrite-derived nitric oxide formation

1.口服亚硝酸盐对循环一氧化氮(NO)的影响1 mg/kg亚硝酸钠对大鼠血液中NO产生的电子顺磁共振(EPR)信号表明，亚硝酸根可以作为HbNO的一种来源。联合服用亚硝酸盐(100 mg/升饮用水)和L(1g/升)3周可显著降低L(10 9±10)毫米汞柱诱发的高血压(14 9±10毫米汞柱)，而单用L硝酸甘油(170±13毫米汞柱)(P<0.0 5)。我们的研究结果清楚地表明，口服亚硝酸盐可以替代L精氨酸作为体内NO的来源。肾缺血再灌注损伤后亚硝酸根的形成静脉输注稳定的亚硝酸根促进肾缺血时Hb^-15&gt；NO的生成，说明NO的来源是亚硝酸盐。我们的研究结果表明，亚硝酸盐可以作为缺血肾脏中NO的替代来源，它与血红蛋白结合，然后在再灌注后通过循环传播。饮食剂量亚硝酸盐衍生的一氧化氮改善L-NAME诱导的高血压大鼠的肾脏损伤慢性给予饮食剂量的亚硝酸盐(1 mg/L)可减轻L-NAME诱导的肾脏病理改变和蛋白尿。高剂量亚硝酸盐(10 mg/L)也可减轻L所致的肾损伤。我们的结论是，当依赖一氧化氮合酶/L精氨酸的一氧化氮生成系统受损时，饮食中亚硝酸盐来源的NO生成系统可能作为NO生成的备用系统。我们的发现可能至少部分解释了富含蔬菜和水果的饮食诱导心血管疾病预防的机制。

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.