The role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning in isolated rat hearts
The role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning in isolated rat hearts
复制标题
DOI：
10.1016/j.ejphar.2005.12.039
复制
发表时间：
2006-02-15
影响因子：
5
通讯作者：
Schoemaker, RG
中科院分区：
文献类型：
--
作者：
Chai, WX;Mehrotra, S;Schoemaker, RG
短暂的冠状动脉闭塞可以保护心脏在随后的长期冠状动脉闭塞过程中免受损害；缺血预处理。在离体灌注大鼠心脏中研究降钙素基因相关肽 (CGRP) 在缺血预适应中的作用，方法是测量缺血预适应期间 CGRP 的释放，并在存在或不存在 CGRP 拮抗剂 BIBN4096BS 的情况下通过外源 CGRP 输注来模拟这一情况。 CGRP 以浓度依赖性方式增加左心室压力和冠状动脉流量，BIBN4096BS 可以有效拮抗这一作用。对大鼠心脏 (n = 36) 进行 45 分钟冠状动脉闭塞和 180 分钟再灌注，在此之前进行：(1) 假预处理，(2) BIBN4096BS 输注 (1 μM)，(3) 通过 15 分钟冠状动脉闭塞和 10 分钟再灌注进行预处理，(4) 与 3 相同，但使用 BIBN4096BS，(5) 15 分钟CGRP 输注 (5 nM) 和 10 分钟冲洗，(6) 与 5 相同，但使用 BIBN4096BS。通过反应性充血、肌酸激酶释放、与危险区域相关的梗塞面积（%）以及左心室压力恢复来评估心脏保护。预处理使冠状动脉流出物中的 CGRP 释放量从 88 +/- 13 增加到 154 +/- 32 pg/min/g，并通过减少反应性充血 (35%)、减少肌酸激酶释放 (53%)、限制梗死面积 (48%) 和改善左心室压力恢复 (36%) 显着保护心脏。外源性 CGRP 诱导类似预处理的心脏保护作用。 BIBN 完全消除了预处理和外源 CGRP 诱导的心脏保护作用。总之，由于预适应诱导的 CGRP 释放的心脏保护作用可以通过外源 CGRP 来模拟，并且两者都可以被 CGRP 拮抗剂阻断，因此结果表明 CGRP 在缺血预适应中的重要作用。 (c) 2005 Elsevier B.V. 保留所有权利。
Brief coronary artery occlusion can protect the heart against damage during subsequent prolonged coronary artery occlusion; ischemic preconditioning. The role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning is investigated in isolated perfused rat hearts, by measuring CGRP release during ischemic preconditioning and mimicking this by exogenous CGRP infusion, either in the absence or presence of the CGRP antagonist BIBN4096BS. CGRP increased left ventricular pressure and coronary flow in a concentration dependent manner, which was effectively antagonized by BIBN4096BS. Rat hearts (n = 36) were subjected to 45 min coronary artery occlusion and 180 min reperfusion, which was preceded by: (1) sham pretreatment, (2) BIBN4096BS infusion (1 mu M), (3) preconditioning by 15 min coronary artery occlusion and 10 min reperfusion, (4) as 3, but with BIBN4096BS, (5) 15 min CGRP infusion (5 nM) and 10 min washout, (6) as 5, but with BIBN4096BS. Cardiac protection was assessed by reactive hyperaemia, creatine kinase release, infarct size related to the area at risk (%), and left ventricular pressure recovery. Preconditioning increased CGRP release into the coronary effluent from 88 +/- 13 to 154 +/- 32 pg/min/g, and significantly protected the hearts by decreasing reactive hyperaemia (35%), reducing creatine kinase release (53%), limiting infarct size (48%), and improving left ventricular pressure recovery (36%). Exogenous CGRP induced preconditioning-like cardioprotection. BIBN completely abolished the cardioprotection induced by preconditioning as well as by exogenous CGRP. In conclusion, since cardioprotection of preconditioning-induced CGRP release can be mimicked by exogenous CGRP, and both can be blocked by a CGRP antagonist, results indicate an important role for CGRP in ischemic preconditioning. (c) 2005 Elsevier B.V. All rights reserved.