Hemodynamic effect of vasoactive peptides on miocardial microvasculature

血管活性肽对心肌微血管的血流动力学影响

• 批准号: 05454691
• 负责人: OHSHIMA Norio
• 金额: $ 4.61万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454691/
• 关键词: myocardium; microcirculatin; calcitonine gene related protein; endothelin-1; Langendorf's perfusion; 心筋、; 微小循環、; エンドセリン、; カルシトニン遺伝子関連ペプチド; 冠循環; 血行力学

Calcitonin gene-related peptide (CGRP), known as a potent vasodilator and a nervemediated vasoactive peptide, is a candidate for a possible physiological antagonist of endothelin-1 (ET-1). Thus, we investigated the pharmacological interactions between ET-1 and CGRP with a special emphasis on the microvascular hemodynamics and the energy-related metabolites in the myocardium.The isolated rat hearts were perfused at a constant flow rate with an oxygenated Krebs-Ringer solution in the Langendorff's perfusion preparation. An intracoronary bolus injection of CGRP into the isolated rat beating heart dose-dependently decreased the coronary perfusion pressure (CPP) precontracted by ET-1 (30 pmole). Vasodilating action of CGRP was about three orders of magnitude potent than that of nitroglycerin and two orders potent than that of isobutylmethylxanthine (IBMX). Ed50 value ET-1 and CGRP was almost comparable in order. Microvascular blood flow was also visualized in the anterior epicardium of the … More left ventricle by means of an intravital fluorescence microscope system. The CGRP (100 pmole) -induced vasodilation of the small-sized arterioles (10-40, um in diameter) was also confirmed by small-sized arterioles (10-40, um in diameter) was also confirmed by the direct intravital microscopic observation (relaxation ratio was 47.1<plus-minus>5.4% (mean<plus-minus>SE,nEnergy-related metabolite contents in the myocardium were measured by means of 31P-nuclear magnetic resonance (31P-NMR) spectroscopy. After ET-1 (30 pmole) plus vehicle administration, high-energy phosphates (phosphocreatine (PCr), ATP) were markedly reduced (44<plus-minus>7%, 17<plus-minus>5%), while myocardial pH decreased by -0.19<plus-minus>0.09. These anaerobic changes in the myocardium as well as macrohemodynamic alterations (increases in CPP,decrease in dP/dt etc.) induced by ET-1 was markedly protected ; 1 by the concomitant administration of CGRP.The decrease in PCr content in the myocardium induced by ET-1 was attenuated by a slight amount of CGRP (100 pmole) significantly (p<We concluded that CGRP effectively protected the endothelin-induced myocardial ischemia both hemodynamically and metabolically in the isolated beating heats of rats. Less

降钙素基因相关肽（CGRP）被认为是一种有效的血管舒张剂和神经介导的血管活性肽，是内皮素-1 （ET-1）可能的生理拮抗剂。因此，我们研究了ET-1和CGRP之间的药理学相互作用，特别强调了微血管血流动力学和心肌中能量相关代谢物。在Langendorff灌注制备中，用含氧Krebs-Ringer溶液以恒定流速灌注离体大鼠心脏。冠状动脉内注射CGRP剂量依赖性地降低ET-1预收缩的冠状动脉灌注压（CPP）（30摩尔）。CGRP的血管扩张作用比硝酸甘油强3个数量级，比异丁基甲基黄嘌呤（IBMX）强2个数量级。Ed50值ET-1与CGRP排序基本相当。通过活体荧光显微镜系统，还可以观察到左心室前心外膜的微血管血流。CGRP（100摩尔）诱导的小微动脉（直径10-40 μ m）的血管舒张也被直接活体显微观察证实（舒张比为47.1<正负b> 5.4%（平均<正负>SE）），心肌能量相关代谢物含量通过31p核磁共振（31P-NMR）谱测定。经ET-1（30摩尔）+载药给药后，心肌中高能磷酸（磷酸肌酸（PCr）、ATP）明显减少（44<正负>7%,17<正负>5%），心肌pH降低-0.19<正负>0.09。ET-1诱导的心肌无氧变化及大血流动力学改变（CPP升高、dP/dt降低等）得到明显保护；1 .同时服用CGRP。少量CGRP（100摩尔）可显著减弱ET-1诱导心肌中PCr含量的下降（p<）。由此可见，CGRP在离体热心肌中对内皮素诱导的心肌缺血具有血流动力学和代谢保护作用。少

项目成果

M.Saito, S.Homma, I.Yamatsu, M.Sato and N.Ohshima: "Visualization of renal microcirculation in isolated Munich-Wistar rat kidneys : Effect of endothelin-1 on renal hemodynamic activity" Jpn.J.Pharmacol. Vol.66. 221-229 (1994)

M.Saito、S.Homma、I.Yamatsu、M.Sato 和 N.Ohshima：“离体慕尼黑 Wistar 大鼠肾脏中肾微循环的可视化：内皮素 1 对肾脏血流动力学活动的影响”Jpn.J.Pharmacol。

S.Homma, T.Miyauchi, N.Tsushima, Y.Sugishita and N.Ohshima: "Effect of calcitonin gene-related peptide on energy metabolism ischemic myocardium." Progress in Microcirculation Research (Eds.H.Niimi et al), Elsevier Science Ltd.145-148 (1994)

S.Homma、T.Miyauchi、N.Tsushima、Y.Sugishita 和 N.Ohshima：“降钙素基因相关肽对缺血性心肌能量代谢的影响”。

K.Furukawa: "Mechanisms of vasospasm induced by endothelin-1 observed in cremaster muscle microcirculation." Microcirculation annual. 10. 73-74 (1994)

K.Furukawa：“在提睾肌微循环中观察到内皮素-1 诱导血管痉挛的机制。”

S.Homma: "Effect of calcitonin gene-related peptide on energy metabolism in ischemic myocardium.In;Progress in Microcirculation Research(Eds.H.Niimi et al.)." Elsevier Science,Oxford(in press),

S.Homma：“降钙素基因相关肽对缺血心肌能量代谢的影响。In；微循环研究进展（Eds.H.Niimi 等人）。”

K.Furukawa K.Yanagi, K.Ookawa.K.Goto, and N.Ohshima: "Mechanisms of vasospasm induced by endothelin-1 observed in cremaster muscle microcirculation." Microcirculation annual 1994 (Eds.M.Tsuchiya et al.), Nihon-Igakukan, Co.Ltd.73-74 (1994)

K.Furukawa K.Yanagi、K.Ookawa.K.Goto 和 N.Ohshima：“在提睾肌微循环中观察到的内皮素 1 诱导血管痉挛的机制。”