Hemodynamic effect of vasoactive peptides on miocardial microvasculature

降钙素基因相关肽(CGRP)是一种强有力的血管扩张剂和神经介导性血管活性多肽，可能是内皮素-1(ET-1)的一种生理拮抗剂。因此，我们研究了ET-1和CGRP之间的药理相互作用，特别是微血管血流动力学和心肌中与能量相关的代谢物。在朗宁多夫的灌流准备中，以恒定的流量用含氧的Krebs-Ringer液灌流大鼠心脏。冠脉内注射降钙素基因相关肽可剂量依赖性地降低ET-1(30pmole)预收缩的冠脉灌注压(CPP)。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和CGRP在顺序上基本相当。在…的前心外膜也可见微血管血流。通过活体荧光显微镜系统获得更多的左心室。CGRP(100pmole)对小动脉(直径10-40um)的血管扩张作用也被小动脉(直径为10-40um)所证实，活体显微镜直接观察也证实了这一点(松弛比为47.1；正负-GT；5.4%(平均值&lt；正负&GT；SE，n能量相关代谢物含量由31P-核磁共振波谱测定)。在ET-1(30pmole)加给药后，高能磷酸盐(磷酸肌酸(PCr)，ATP)显著减少(44&lt；+-gt；7%，17&lt；+-gt；5%)，而心肌pH下降-0.19；+&gt；0.09。这些心肌无氧变化以及宏观血流动力学改变(CPP升高，dp/dt降低等)。小剂量的CGRP(100pmole)可显著减轻ET-1诱导的大鼠心肌PCr含量的下降(p<0.05)。结论：CGRP对内皮素诱导的大鼠心肌缺血有明显的血流动力学和代谢保护作用。较少

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