A new role of NO on the accelerating effect of oxygen supply to tissue

NO 在加速组织供氧方面的新作用

• 批准号: 08457012
• 负责人: KOSAKA Hiroaki
• 金额: $ 4.54万
• 依托单位: Kagawa Medical University (1997)Osaka University (1996)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457012/
• 关键词: nitric oxide; hemoglohin; oxygen relrease; ESR; EPR; nitroglycerin; isosobide dinitrate; angina; 一酸化窒素

The effect of nitroglycerin on oxygen (O2) release in microcirculation was investingated by examining single, unbranched hepatic sinusoids of rats using dual-spot microspectroscopy. Nitroglycerin significantly increased O2 selease from erythrocytes flowing in the sinusoids. Differences in O2 saturation of hemoglobin per unit length of the sinusoid were significantly enhanced, while there were no significant changes in erythrocyte velocity, hemoglobin (Hb) concentration, and oxyhemoglobin flow into the sinusoids, as well as regional hepatic blood flow measured with a laser tissue blood flow meter. No change was noted for hepatic O2 consumption measured in isolated liver perfused with Hb-free oxygenated buffer. Isosorbide denitrate showed a similar but slower effect. These findings suggest that nitroglycerin and isosorbide dinitrate enhance O2 release from erythrocytes without significantly increasing tissue blood flow. In vitro study revealed O2 affinity was significantly decreased in blood taken from rats treated with nitroglycerin. It contained NO bound to Hb a subunit alone. It is possible that breaking or stretching of the NO heme iron-proximal histidine bond during organ circulation triggered the decrease in O2 affinity, while the O2 affinity was recovered in lung by restoring the bond. These results should operate when cytokines induce NO synthase in vascular system during such events as inflammation.

通过使用双点显微光谱检查大鼠的单个、无分支的肝窦来研究硝酸甘油对微循环中氧气（O2）释放的影响。硝酸甘油显着增加血窦中流动的红细胞释放氧气。血窦单位长度血红蛋白的O2饱和度差异显着增强，而红细胞速度、血红蛋白（Hb）浓度、进入血窦的氧合血红蛋白流量以及激光组织血流量计测量的区域肝血流量没有显着变化。在用无 Hb 含氧缓冲液灌注的离体肝脏中测量的肝 O2 消耗没有变化。硝酸异山梨酯表现出类似但较慢的效果。这些发现表明，硝酸甘油和硝酸异山梨酯可增强红细胞的 O2 释放，而不会显着增加组织血流量。体外研究表明，接受硝酸甘油处理的大鼠血液中的 O2 亲和力显着降低。它仅含有与 Hb 亚基结合的 NO。器官循环过程中，NO 血红素铁-近端组氨酸键的断裂或拉伸可能引发 O2 亲和力下降，而肺中的 O2 亲和力则通过恢复该键而恢复。当细胞因子在炎症等事件期间诱导血管系统中的一氧化氮合酶时，这些结果应该起作用。

项目成果

K.Okada, Y.Nishida, H.Murakami, I.Sugimoto, H.Kosaka, H.Morita, C.Yamashita, M.Okada: "A Role of Endogenous Endothelin in the Development of Graft Arteriosclerosis in Rat Cardiac Allografts : Anti-Proliferative Effects of a Nonselective Endothelin Recepto

K.Okada、Y.Nishida、H.Murakami、I.Sugimoto、H.Kosaka、H.Morita、C.Yamashita、M.Okada：“内源性内皮素在大鼠同种异体心脏移植物动脉硬化发展中的作用：抗

H.Kosaka: "Physiological role of nitric oxide as an enhancer of oxygen transfer from erythrocytes to tissues" Biochem.Biopys.Res.Commun.218. 749-752 (1996)

H.Kosaka：“一氧化氮作为氧从红细胞转移到组织的增强剂的生理作用”Biochem.Biopys.Res.Commun.218。

A.Seiyama: "Effect of acetylcholine and calmodulin-inhibitor on O2 transfer from exocrine pancreatic microvessels of rats." Am.J.Physiol. 271. H1-H7 (1996)

A.Seiyama：“乙酰胆碱和钙调蛋白抑制剂对大鼠外分泌胰腺微血管 O2 转移的影响。”

S.Shimizu: "Induction of ICE family proteases in apoptosis induced by reoxygenation of hypoxic hepatocytes" Am.J.Physiol. 271. G949-G958 (1996)

S.Shimizu：“在缺氧肝细胞复氧诱导的细胞凋亡中诱导 ICE 家族蛋白酶”Am.J.Physiol。

J.Igarashi: "Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes" Am.J.Physiol. 43. C245-C252 (1998)

J.Igarashi：“诱导型一氧化氮合酶增强大鼠心肌细胞氧化应激引起的损伤”Am.J.Physiol。