A Study on the Regulation of CoronaryBlood Flow in the condition of Inhabited Synthesis of Endothelium-Derived Nitric Oxide

内皮源一氧化氮抑制合成条件下冠状动脉血流调节的研究

• 批准号: 08670806
• 负责人: OKUMURA Ken
• 金额: $ 1.41万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-08670806/
• 关键词: nitric oxide; endothelium; coronary blood flow; adenosine; oxygen radicals; reactive hyperemia; L-arginine

To clarify the role of endothelium-derived nitric oxide (EDNO) on the regulation of coronary blood flow, we performed in-vivo studies in anesthetized dogs. It was revealed that EDNO plays a role in the regulation of the basal coronary blood flow (Arch int Pharmacodyn 1994 ; 327 : 251-265), and that myocardial reactive hyperemia (RH) is mediated not only by adenosine but by EDNO (Am J Physiol 1992 ; 263 : H4-H14). Recently, we examined the effect of manganese (Mn)-superoxide dismutase (SOD) on RH in anesthetized dogs, and revealed superoxide redicals generated during ischemia for 60s and reperfusion attenuates myocardial RH through inactivation of EDNO (Cardiovascular Res 1996 ; 31 : 537-545).It was also shown that Mn-SOD shows more beneficial effects on myocardial RH than Cu, Zn-SOD.We also showed that when NO synthesis is inhibited by L-arginine analogue, LNAME,adenosine release is increased in response to the myocardial oxygen demand and with this compensatory adenosine release, coronary flow is increased and ventricular function is unaffected (Am J Physiol 1996 ; 270 : H427-H434). Chronic inhibition of NO formation with oral administration of L-NAME for 4 weeks blunted coronary reactive hyperemia but did not substantially impair the coronary blood flow response to the increased myocardial oxygen requirement produced by atrial pacing. It was therefore indicated that adenosine is likely to play a role also in chronic model of NO synthesis inhibition (Jpn Cric J,1998, in press).

为了阐明内皮源性一氧化氮（EDNO）在调节冠状动脉血流中的作用，我们对麻醉的狗进行了体内研究。研究发现EDNO在调节冠状动脉基底血流中起作用（Arch int Pharmacodyn 1994; 327: 251-265），心肌反应性充血（RH）不仅由腺苷介导，而且由EDNO介导（Am J Physiol 1992; 263: H4-H14）。最近，我们研究了锰(Mn)-超氧化物歧化酶（SOD）对麻醉犬RH的影响，发现缺血60秒和再灌注过程中产生的超氧化物残留通过使EDNO失活而减弱心肌RH （Cardiovascular Res 1996; 31: 537-545）。Mn-SOD对心肌RH的改善作用优于Cu、Zn-SOD。我们还发现，当l -精氨酸类似物LNAME抑制NO合成时，腺苷释放会随着心肌需氧量的增加而增加，随着这种代偿性腺苷释放，冠状动脉血流增加，心室功能不受影响（Am J Physiol 1996; 270: H427-H434）。口服L-NAME 4周对NO形成的慢性抑制可减弱冠状动脉反应性充血，但并未实质性损害冠状动脉血流对心房起搏引起的心肌需氧量增加的反应。因此表明腺苷可能在NO合成抑制的慢性模型中也发挥作用（Jpn Cric J,1998, in press）。

项目成果

Naoyuki Suto: "Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency" Am J Physiol. (in press). (1998)

Naoyuki Suto：“一氧化氮调节心肌收缩力和耗氧量而不改变收缩效率”Am J Physiol。

Shinji-Tayama: "INFLUENCE OF CHIRONIC NITRIC OXIDE INHIBITION TO CORONARY BLOOD FLOW REGULATION" Jpn Clirc J. (in press). (1998)

Shinji-Tayama：“手性一氧化氮抑制对冠状动脉血流调节的影响”Jpn Clirc J.（出版中）。

Matsunaga T,Okumura K,Ishzaka H,et al.: "Effect of cumulative dose of NG-nitro-L-arginine methyl ester on coronary blood flow of anesthetized and conscious dogs." Arch Int Pharamacody. 327. 251-265 (1994)

Matsunaga T、Okumura K、Ishzaka H 等人：“NG-硝基-L-精氨酸甲酯累积剂量对麻醉和清醒狗冠状动脉血流的影响”。

Okumura K,Yasue H,Fujii H,et al.: "Effects of brain (B-type) natriuretic peptide on cornary artery diameter and coronary hemodynamic variables in humans : Comparison with effects on systemic hemodynnamic variables." J Am Cardiol. 25. 342-348 (1995)

Okumura K、Yasue H、Fujii H 等人：“脑（B 型）利钠肽对人类角膜动脉直径和冠状动脉血流动力学变量的影响：与对全身血流动力学变量的影响进行比较。”

Ryusuke Tsunoda: "Enhancement of myocardial reactive hyperemia with manganese-superoxide dismutase:role of endothelium-derived nitric" Cardiovascular Research. 31. 537-545 (1996)

Ryusuke Tsunoda：“锰超氧化物歧化酶增强心肌反应性充血：内皮衍生的硝酸的作用”心血管研究。