GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta through a pathway involving KATP and cAMP
GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta through a pathway involving KATP and cAMP
复制标题
DOI：
10.1016/j.abb.2008.08.001
复制
发表时间：
2008-10-15
影响因子：
3.9
通讯作者：
Grieve, David J.
中科院分区：
文献类型：
--
作者：
Green, Brian D.;Hand, Katharine V.;Grieve, David J.
越来越多的临床和实验研究表明，胰岛素释放激素胰高血糖素样肽-1(GLP-1)可能对心血管系统起到额外的保护/修复作用。本研究的目的是观察GLP-1(7-36)酰胺、三种结构相关多肽和一种非肽GLP-1激动剂对大鼠主动脉的舒血管作用。有趣的是，所有的GLP-1化合物，包括已建立的GLP-1受体拮抗剂exendin(9-39)，都能引起浓度依赖性的松弛。使用超极化浓度的钾或格列本脲的机制研究表明，这些松弛效应是通过对ATP敏感的钾通道的特异性激活而介导的。使用一种特定的膜通透性环腺苷酸(CAMP)拮抗剂的进一步实验，以及对GLP-1反应增加cAMP产生的证明，表明了这一途径的关键重要性。这些数据大大扩展了先前关于GLP-1可能调节血管功能的观察结果，并表明这种作用可能是由GLP-1受体介导的。然而，还需要进一步的研究来确定GLP-1相关药物是否可以为糖尿病患者带来额外的心血管益处。(C)2008 Elsevier Inc.保留所有权利。
increasing evidence from both clinical and experimental studies indicates that the insulin-releasing hormone, glucagon-like peptide-1 (GLP-1) may exert additional protective/reparative effects on the cardiovascular system. The aim of this study was to examine vasorelaxant effects of GLP-1(7-36)amide, three structurally-related peptides and a non-peptide GLP-1 agonist in rat aorta. Interestingly, all GLP-1 compounds, including the established GLP-1 receptor antagonist, exendin (9-39) caused concentration-dependent relaxation. Mechanistic studies employing hyperpolarising concentrations of potassium or glybenclamide revealed that these relaxant effects are mediated via specific activation of ATP-sensitive potassium channels. Further experiments using a specific membrane-permeable cyclic AMP (cAMP) antagonist, and demonstration of increased cAMP production in response to GLP-1 illustrated the critical importance of this pathway. These data significantly extend previous observations suggesting that GLP-1 may modulate vascular function, and indicate that this effect may be mediated by the GLP-1 receptor. However, further studies are required in order to establish whether GLP-1 related agents may confer additional cardiovascular benefits to diabetic patients. (c) 2008 Elsevier Inc. All rights reserved.