Physiological and pathophysiological role of nitrite-derived nitric oxide formation

亚硝酸盐衍生的一氧化氮形成的生理和病理生理作用

• 批准号: 17390066
• 负责人: TAMAKI Toshiaki
• 金额: $ 9.34万
• 依托单位: The university of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390066/
• 关键词: Nitrite; Nitric oxide; L-NAME; HbNO signal; Electron Paramagnetic Resonance; Ischemic renal injury

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.

1.经口给予亚硝酸盐对循环一氧化氮（NO）的影响当大鼠经口给予1 mg/kg Na^NO_2时<15>，<15>在血液中观察到明显的Hb^NO衍生的二重态电子顺磁共振（EPR）信号，这表明经口给予的亚硝酸盐可以作为HbNO的形式成为循环NO的来源。亚硝酸盐（100 mg/L饮用水）与L-NAME（1 g/L）联合给药3周，与单独使用L-NAME（170 ± 13 mmHg）相比，显著减轻了L-NAME诱导的高血压（149 ± 10 mmHg）。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源性NO的形成静脉输注稳定同位素[^<15>N]亚硝酸盐可促进肾缺血时Hb^ NO的形成<15>，证明NO的来源是亚硝酸盐。我们的研究结果表明，亚硝酸盐可以成为缺血肾脏中NO的替代来源，并且它与血红蛋白结合，然后在再灌注后通过循环传播。3.饮食中亚硝酸盐衍生的一氧化氮可改善L-NAME诱导的高血压大鼠肾损伤慢性给予饮食中亚硝酸盐（1 mg/L）可减轻L-NAME诱导的肾组织学改变和蛋白尿。高浓度亚硝酸盐（10 mg/L）也可减轻L-NAME引起的肾损伤。我们的结论是，膳食亚硝酸盐衍生的NO生成系统可能作为NO生成的备份系统时，NOS/L-精氨酸依赖的NO生成系统受到损害。我们的研究结果可以解释，至少部分，丰富的蔬菜和水果的饮食诱导预防心血管疾病的机制。

项目成果

ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells

• DOI: 10.1016/j.yexcr.2005.04.028
• 发表时间: 2005-08-15
• 期刊: EXPERIMENTAL CELL RESEARCH
• 影响因子: 3.7
• 作者: Izawa, Y;Yoshizumi, M;Tamaki, T
• 通讯作者: Tamaki, T

Effects of angiotensin II type 1 receptor blockade on the systemic blood NO dynamics in L-NAME-treated rats

血管紧张素 II 1 型受体阻断对 L-NAME 治疗大鼠全身血液 NO 动态的影响

• 发表时间: 2006
• 期刊: Hypertension Research 29
• 作者: Zhang;J.;Hosoya;T.;Maruyama;A.;Nishikawa K.;Maher;J.M.;Ohta;T.;Motohashi;H.;Fukamizu;A.;Shibahara;S.;Itoh;K.;Yamamoto;M.;Yasuhisa Kanematsu
• 通讯作者: Yasuhisa Kanematsu

Calcium and reactive oxygen species mediated zinc-induced apoptosis in PC12 cells

钙和活性氧介导锌诱导的 PC12 细胞凋亡

• 发表时间: 2006
• 期刊: J.Pharmacol Science 102
• 作者: Mukai;H.Y.;Motohashi;H.;Ohneda;O.;Suzuki;N.;Nagano;M.;Yamamoto;M.;Shinji Abe
• 通讯作者: Shinji Abe

Nitrite-drives nitric oxide formation following ischemia-reperfusion injury in kidney.

肾脏缺血再灌注损伤后亚硝酸盐驱动一氧化氮形成。

• 发表时间: 2005
• 期刊: Am. J. Physiol. Renal Physiol. 288
• 作者: Okawa;H.;Motohashi;H.*;Kobayashi;A.;Aburatani;H.;Kensler T.W.;Yamamoto;M.;Masumi Okamoto
• 通讯作者: Masumi Okamoto

Nitrite is an alternative source of NO in vivo.

• DOI: 10.1152/ajpheart.00525.2004
• 发表时间: 2005-05
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: K. Tsuchiya;Y. Kanematsu;M. Yoshizumi;Hideki Ohnishi;K. Kirima;Yuki Izawa;Michiyo Shikishima;T. Ishida;Shuji Kondo;S. Kagami;Y. Takiguchi;T. Tamaki