IN Vivo Study on Coronary Circulation Under Pharmacologic Inhibition of Endothelium-Derived Relaxing Factor

内皮源性舒张因子药理抑制下冠状动脉循环的体内研究

• 批准号: 02670401
• 负责人: OKUMURA Ken
• 金额: $ 1.41万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670401/
• 关键词: Endothelium; Nitric oxide; L-arginine; Acetylcholine; Coronary circulation; Reactive hyperemia; N^G-monomethyl-L-arginine; adenosine; Endothelium; Nitric oxide; Acetylcholine; N^GーmonomethylーLーarginine; Coronary blood flow; Adenosine; Lーargi

(1) Endothelium-derived nitric oxide (EDNO) as a mediator of acetylcholine (ACh)-induced coronary vasodilation in dogs : To investigate the role of EDNO in regulation of the tonus of the coronary artery system in vivo, the effect of N^G-monomethyl-L-arginine (NMA), a specific inhibitor of the synthesis of NO L-arginine, on ACh-induced coronary vasodilation was examined in open-chest, pentobarbital-anesthetized dogs. At baseline, the infusion of ACh and adenosine into the left circumflex artery (LCX) increased the LCX blood flow. Continuous infusion of NMA into LCX significantly attenuated ACh-induced increase in the LCX flow. NMA showed no effect on adenosine-induced increase in the LCX flow. After the NMA infusion was terminated, the effect of ACh partially returned to the baseline level. In other dogs, L-arginine was administered just after the NMA infusion, Which Completely reversed the inhibitory effect of NMA on ACh-induced vasodilation. Thus EDNO is a mediator of ACh-induced vaso … More dilation of the coronary resistance vessels in dogs.(2) Role of endothelium-derived nitric oxide (EDNO) in myocardial reactive hyperemia : In pentobarbital-anesthetized dogs, we investigated the role of the EDNO and adenosine in the regulation of the coronary blood flow during myocardial reactive hyperemia. Repayment of flow debt following 10-, 20-, and 60-second occlusion of the left circumflex artery )LCX) were measured before and after infusion of N^G-monomethyl-L-arginine (NMA), 8-phenyl-theophylline (8-PT) and both NMA and 8-PT in to the LCX. Infusion of NMA significantly reduced repayments of flow debt following 10-, 20-, and 60-second LCX occlusion by means of 30%, 34% and 14%, respectively. Infusion of 8-PT also reduced these repayments of flow debt significantly by means of 31%, 30% and 34%, respectively. Simultaneous infusion of NMA and 8-PT significantly attenuated the peak reactive flow rate and reduced repayment of flow debt following 20-second LCX occlusion by a mean of 57%, and this reduction was significantly greater than each of those by the individual administration of NMA and 8-PT. The suppressive effect of NMA on repayment of flow debt was quickly reversed by the infusion of L-arginine. These results indicate that the myocardial reactive hyperemia is regulated not only by adenosine, but also by the EDNO. Less

(1)内皮源性一氧化氮（EDNO）作为乙酰胆碱（ACh）诱导的犬冠状动脉血管舒张的介质：为了研究EDNO在体内冠状动脉系统张力调节中的作用，在开胸、戊巴比妥麻醉的犬中检查了NO-L-精氨酸合成的特异性抑制剂--N，G-单甲基-L-精氨酸（NMA）对ACh诱导的冠状动脉血管舒张的作用。在基线时，将ACh和腺苷输注到左回旋支（LCX）中增加了LCX血流量。NMA持续注入LCX可显著减弱ACh诱导的LCX流量增加。NMA对腺苷诱导的LCX流量增加无影响。停止NMA输注后，ACh的作用部分恢复至基线水平。在另一些犬中，在输注NMA后立即给予L-精氨酸，可完全逆转NMA对ACh引起的血管舒张的抑制作用。因此EDNO是ACh诱导的血管紧张素转换酶抑制剂。 ...更多信息 扩张犬的冠状动脉阻力血管。(2)内皮源性一氧化氮（EDNO）在心肌反应性充血中的作用：在戊巴比妥麻醉犬中，我们研究了EDNO和腺苷在心肌反应性充血期间对冠状动脉血流量的调节中的作用。在将N，N-二甲基-L-精氨酸（NMA）、8-苯基-茶碱（8-PT）以及NMA和8-PT两者输注至LCX之前和之后测量左回旋支动脉（LCX）闭塞10秒、20秒和60秒后的流债偿还。NMA的输注显著降低了10秒、20秒和60秒LCX闭塞后的血流债偿还，分别为30%、34%和14%。输注8-PT也分别通过31%、30%和34%显著降低了这些流动债务的偿还。同时输注NMA和8-PT可显着减弱峰值反应性流速，并将20秒LCX闭塞后的流量债偿还平均减少57%，并且这种减少明显大于单独注射NMA和8-PT的减少。NMA对流动债务偿还的抑制作用很快被L-精氨酸的输注所逆转。这些结果表明，心肌反应性充血不仅受腺苷的调节，而且还受EDNO的调节。少

项目成果

Ken Okumura,et al.: "Effect of Hー1 receptor stimulation on coronary artery diameter in patients with variant angina.Comparison with effect of acetylcholine." Journal of the American College of Cardiology. 17. (1991)

Ken Okumura 等人：“H-1 受体刺激对变异性心绞痛患者冠状动脉直径的影响。与乙酰胆碱的影响比较。《美国心脏病学会杂志》17。（1991 年）。

Ken Okumura,et al.: "A study on cornary hemodynamics during acetylcholine-induced coronary spasm in patients with variant angina.Endothelium-dependent dilation in the resistance vessels" Journal of the American College of Cardiology. 19. (1992)

Ken Okumura 等人：“变异型心绞痛患者乙酰胆碱诱导的冠状动脉痉挛期间的角膜血流动力学研究。阻力血管内皮依赖性扩张”美国心脏病学会杂志。

Ogawa H, Yasue H, Misumi I, Masuda T, Okumura K, et al.: "Plasma platelet-derived growth factor levels in coronary circulation in unstable angina pectoris." Am J Cardiol. 69. 453-456 (1992)

Okawa H、Yasue H、Misumi I、Masuda T、Okumura K 等人：“不稳定型心绞痛冠状动脉循环中血浆血小板衍生生长因子的水平。”

Yamabe H, Okumura K, Ishizaka H, et al.: "Role of endothelium-derived nitric oxide in myocardial reactive hyperemia." Am J Physiology : Heart and Circulatory Physiology.(1992)

Yamabe H、Okumura K、Ishizaka H 等人：“内皮源性一氧化氮在心肌反应性充血中的作用”。

泰江 弘文,奥村 謙: "アセチルコリンと冠動脈の攣縮" 実験医学. 8. 2284-2288 (1990)

Hirofumi Yasue，Ken Okumura：“乙酰胆碱和冠状动脉痉挛”实验医学 8. 2284-2288 (1990)。