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

肾脏缺血再灌注损伤后亚硝酸盐源性一氧化氮的形成及其病理生理作用

• 批准号: 16590196
• 负责人: TSUCHIYA Koichiro
• 金额: $ 2.24万
• 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 (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590196/
• 关键词: nitrite; ischemia; kidney; electron paramagnetic resonance; EPR; nitric oxide; NO; 安定同位体

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.

一氧化氮（NO）具有多种生理功能，一氧化氮合酶（NOS）通过催化L-精氨酸的氧、四氢生物蝶呤和NADPH依赖性氧化来产生NO，亚硝酸盐和硝酸盐被认为是NO的废物形式。我们假设口腔中的亚硝酸盐被分解为NO，这种NO分布到血液中并在体内发挥生理作用。在本研究中，我们使用电子顺磁共振（EPR）光谱测量了作为全血中循环NO指标的血红蛋白（Hb）-NO，并显示了肾缺血再灌注损伤中亚硝酸盐衍生的NO形成。<结果>1.静脉输注亚硝酸钠促进了肾缺血期间HbNO的形成，这表明： NO的来源是亚硝酸盐。2.肾脏缺血40分钟后出现HbNO的EPR信号，肾再灌注使肾脏中的HbNO水平降低，而血液中的HbNO水平相反升高。3.HbNO的量依赖于亚硝酸盐浓度，而这种形成与NOS无关。4.L-NAME治疗三周导致收缩压和血压显着升高。 亚硝酸钠 (1000mg/L) 的共同给药减轻了 L-NAME 诱发的高血压（L-NAME ；170+/-11mmHg vs L-NAME+亚硝酸盐；141+/-16mmHg）。此外，亚硝酸盐与L-NAME共同给药可减轻L-NAME诱导的肾脏组织学变化。这些结果表明，口服亚硝酸盐可增加循环NO，并可能在保护肾脏缺血再灌注损伤方面发挥重要的生理作用。

项目成果

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

Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in kidney

肾脏缺血再灌注损伤后亚硝酸盐衍生的一氧化氮的形成

• 发表时间: 2005
• 期刊: American Journal of Physiology, Renal Physiology 288・1
• 作者: 木村 晋也(筆頭);湯浅 健(5番目);湯浅 健;湯浅 健(金倉 譲編著);Essam Elsamman;Oka N;Hirofumi Izaki;Manabu Sakaki;Essam Elsamman;Tomoharu Fukumori;Hirofumi Izaki;Essam Elsamman;Essam Elsamman;Oka N;Hirofumi Izaki;Manabu Sakaki;Essam Elsamman;Tomoharu Fukumori;Essam Elsamman;Essam Elsamman;Fukumori T;Oka N;Yang XJ;Shimura T;Oka N;Shimura T;Yang XJ;Takahashi M;Inoue Y;Takahashi M;Okamoto M
• 通讯作者: Okamoto M

Formation of systemic hemoglobin-nitric oxide complex (HbNO) from dietary nitrite

从膳食亚硝酸盐形成全身血红蛋白-一氧化氮复合物 (HbNO)

• 发表时间: 2004
• 期刊: J Pharmacol Sci. 96
• 作者: Tsuchiya;K.;M.Okamoto;Tsuchiya K.
• 通讯作者: Tsuchiya K.