Physiological and pathophysiological role of nitrite-derived nitric oxide formation

1. 口服亚硝酸盐对循环一氧化氮的影响。当大鼠口服1 mg/kg Na^<15>NO_2时，在血液中观察到标记Hb^<15>NO衍生的双电子顺磁共振（EPR）信号，表明口服亚硝酸盐可以作为HbNO的一种形式作为循环NO的来源。亚硝酸盐（100毫克/升饮用水）与L-NAME（1克/升）联合给药3周，与L-NAME单独给药（170±13毫米汞柱）相比，L-NAME诱导的高血压（149±10毫米汞柱）明显减弱。我们的研究结果清楚地表明，口服摄入的亚硝酸盐可以替代l -精氨酸作为体内NO的来源。肾缺血再灌注损伤后亚硝酸盐来源NO的形成静脉输注稳定同位素[^<15>N]亚硝酸盐促进了肾缺血时Hb^<15>NO的形成，说明NO的来源是亚硝酸盐。我们的研究结果表明，亚硝酸盐可能是缺血肾脏一氧化氮的另一种来源，并与血红蛋白结合，然后在再灌注后通过循环扩散。膳食剂量亚硝酸盐（1mg/L）可减轻L- name诱导的肾组织改变和蛋白尿。高剂量亚硝酸盐（10mg/L）对L- name引起的肾损伤也有一定的减轻作用。综上所述，当NOS/ l -精氨酸依赖的NO生成系统受损时，膳食亚硝酸盐衍生的NO生成系统可能作为NO生成的备用系统。我们的发现可以解释，至少在一定程度上，蔬菜和水果丰富的饮食诱导预防心血管疾病的机制。

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.