1997 Fiscal Year Annual Research Report

臓器への酸素供給を促進する内皮由来弛緩因子の新たな役割

Research Project

Project/Area Number	08457012
Research Institution	Kagawa Medical University
Principal Investigator	小坂博昭香川医科大学, 医学部, 教授 (60158897)
Co-Investigator(Kenkyū-buntansha)	米山弘人香川医科大学, 医学部, 助手 (80294750) 精山明敏大阪大学, 医学部, 助手 (70206605)
Keywords	一酸化窒素(NO) / ヘモグロビン / 酸素放出 / 顕微分光 / 狭心症 / ニトログリセリン / 硝酸イソソルビド / 電子スピン共鳴
Research Abstract	臓器循環において、NOが血液から組織への酸素放出を促進させる可能性を検討した。ニトログリセリンや硝酸イソソルビドを投入したラットからの血液中には電子スピン共鳴でNOヘモグロビンを検出した。このようなNOヘモグロビンを含むラット血液の酸素解離曲線を検討したところ、ヘモグロビンと酸素との結合力が弱まっていることを初年度に初めて明らかにしている。今年度はin vivoで検討した。狭心症の特効薬であるニトロ系冠拡張薬の作用は、血管を拡張し心負荷を軽減することにあると思われてきた。新たに、一本の毛細血管でみた血液から組織への酸素放出が、その血管での血流増加によらずに、ニトロ系冠拡張薬によって有意に増加することを初めて明らかにした。枝分かれのない単一の肝類洞の2点で、酸素飽和度、赤血球速度、ヘモグロビン濃度を顕微分光装置で計測し、酸素放出速度を求めた。ニトログリセリンは酸素放出を急速に促進した。硝酸イソソルビドの酸素放出促進効果は持続的で長時間作動型の特徴と一致するものであった。この理由として2点間での酸素飽和度の差の有意な増加のみを観測した。オキシヘモグロビン流入量や肝の代謝の増加はなかった。これらの結果は、末梢組織で酸素を放出するときに、一個のNOが結合したHb四量体は、そのHb四量体の他のヘムに結合した酸素をより強く放出する可能性を示唆する。今回のデータは狭心症に対するニトロ系冠拡張薬の作用機構に対し核心的な資料のひとつとなるものと考える。

Research Products
(18 results)

All Other

All Publications (18 results)

[Publications] H.Kosaka: "Elevation of oxygen release by nitroglycerin without increase in blood flow in hepatic microcirculation" Nature Medicine. 3(4). 456-459 (1997)
[Publications] K.Node: "Amelioration of ischemia-and reperfusion-induced myocardial injury by 17betaestradiol" Circulation. 96. 1953-1963 (1997)
[Publications] T-P.Huang: "Role of nitric oxide oxygen transport in hepatic sinusoids during endotoxemia" Hepatology. 26. 336-342 (1997)
[Publications] K.Node: "Effect of acute dynamic exercise on circulating plasma nitric oxide level and correlation to norepinephrine release in normal subjects." Am.J.Cardiol. 79. 526-528 (1997)
[Publications] Node-K: "Reversible reduction in plasma concentration of nitric oxide induced by cigarette smoking in young adults." Am.J.Cardiol. 79(11). 1538-1541 (1997)
[Publications] K.Node: "Bradykinin mediation of Ca2+ activated K+ channels regulates coronary blood flow in ischemic myocardium" Circulation. 95. 1560-1567 (1997)
[Publications] T.Mizuta: "Increased nitric oxide levels in exhaled air of rat lung allografts" J.Thorac.Cardiovasc.Surg. 113. 830-835 (1997)
[Publications] Node-K: "Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension" Hypertension. 30(3ptl). 405-408 (1997)
[Publications] Kosaka H: "Absence of mast cell involvement in leukocyte adhesion and emigration induced by inhibitio of nitric oxide synthase" Lab Inves. 77. 575-580 (1997)
[Publications] K.Node: "Roles of NO and Ca2+-activated K+channels in coronary vasodilation induced by 17betaestradiol in ischemic heart failure" FASEB J. 11. 793-799 (1997)
[Publications] T.Yamamoto: "Increase in experimental pulmonary metastasis in mice by L-arginine under inhibition of nitric oxide productionby NG-nitro-L-arginine methyl ester" Int.J.Cancer. 75. 140-144 (1998)
[Publications] J.Igarashi: "Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes" Am.J.Physiol. 43. C245-C252 (1998)
[Publications] Hiroshi Murakami: "Blockade of nuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit" Am.J.Physiol. 43. R181-186 (1998)
[Publications] I.Sugimoto: "The gain of the hepatorenal reflex in anesthetized dogs" J.Auton.Nerv.Syst. (in press).
[Publications] Y.Ogawa: "Stability of mutant superoxide dismutase-1 associated with familial amyotrophic lateral sclerosis determines the manner of copper release and induction of thioredoxin in erythrocytes" Biochem.Biopys.Res.Commun. 241. 251- (1997)
[Publications] Q.H.Chen: "Sinoaortic denervation enhances sodium retention and mild hypertention in Dahl saltsensitive rats" J.Auton.Nerv.Syst. (in press).
[Publications] H.Kosaka: "Increased oxygen dissociation by nitric oxide from RBC" Adv.Exp.Med.Biol. 19. 349-354 (1998)
[Publications] K.Okada: "Role of Endogenous Endothelin in the Development of Graft Arteriosclerosis in Rat Cardiac Allografts;Anti-Proliferative Effects of a Nonselective Endothelin Receptor Antagonist,Bosentan" Circulation. (in press).

1997 Fiscal Year Annual Research Report

臓器への酸素供給を促進する内皮由来弛緩因子の新たな役割

Principal Investigator

小坂 博昭 香川医科大学, 医学部, 教授 (60158897)

Research Products

[Publications] H.Kosaka: "Elevation of oxygen release by nitroglycerin without increase in blood flow in hepatic microcirculation" Nature Medicine. 3(4). 456-459 (1997)

[Publications] K.Node: "Amelioration of ischemia-and reperfusion-induced myocardial injury by 17betaestradiol" Circulation. 96. 1953-1963 (1997)

[Publications] T-P.Huang: "Role of nitric oxide oxygen transport in hepatic sinusoids during endotoxemia" Hepatology. 26. 336-342 (1997)

[Publications] K.Node: "Effect of acute dynamic exercise on circulating plasma nitric oxide level and correlation to norepinephrine release in normal subjects." Am.J.Cardiol. 79. 526-528 (1997)

[Publications] Node-K: "Reversible reduction in plasma concentration of nitric oxide induced by cigarette smoking in young adults." Am.J.Cardiol. 79(11). 1538-1541 (1997)

[Publications] K.Node: "Bradykinin mediation of Ca2+ activated K+ channels regulates coronary blood flow in ischemic myocardium" Circulation. 95. 1560-1567 (1997)

[Publications] T.Mizuta: "Increased nitric oxide levels in exhaled air of rat lung allografts" J.Thorac.Cardiovasc.Surg. 113. 830-835 (1997)

[Publications] Node-K: "Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension" Hypertension. 30(3ptl). 405-408 (1997)

[Publications] Kosaka H: "Absence of mast cell involvement in leukocyte adhesion and emigration induced by inhibitio of nitric oxide synthase" Lab Inves. 77. 575-580 (1997)

[Publications] K.Node: "Roles of NO and Ca2+-activated K+channels in coronary vasodilation induced by 17betaestradiol in ischemic heart failure" FASEB J. 11. 793-799 (1997)

[Publications] T.Yamamoto: "Increase in experimental pulmonary metastasis in mice by L-arginine under inhibition of nitric oxide productionby NG-nitro-L-arginine methyl ester" Int.J.Cancer. 75. 140-144 (1998)

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

[Publications] Hiroshi Murakami: "Blockade of nuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit" Am.J.Physiol. 43. R181-186 (1998)

[Publications] I.Sugimoto: "The gain of the hepatorenal reflex in anesthetized dogs" J.Auton.Nerv.Syst. (in press).

[Publications] Y.Ogawa: "Stability of mutant superoxide dismutase-1 associated with familial amyotrophic lateral sclerosis determines the manner of copper release and induction of thioredoxin in erythrocytes" Biochem.Biopys.Res.Commun. 241. 251- (1997)

[Publications] Q.H.Chen: "Sinoaortic denervation enhances sodium retention and mild hypertention in Dahl saltsensitive rats" J.Auton.Nerv.Syst. (in press).

[Publications] H.Kosaka: "Increased oxygen dissociation by nitric oxide from RBC" Adv.Exp.Med.Biol. 19. 349-354 (1998)

[Publications] K.Okada: "Role of Endogenous Endothelin in the Development of Graft Arteriosclerosis in Rat Cardiac Allografts;Anti-Proliferative Effects of a Nonselective Endothelin Receptor Antagonist,Bosentan" Circulation. (in press).

小坂博昭香川医科大学, 医学部, 教授 (60158897)