GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta through a pathway involving KATP and cAMP

• Published in: Archives of biochemistry and biophysics 2008-10, Vol.478 (2), p.136-142
• Main Authors: Green, Brian D, Hand, Katharine V, Dougan, Janette E, McDonnell, Bronagh M, Cassidy, Roslyn S, Grieve, David J
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; Cyclic AMP - physiology; DNA Primers - genetics; Gene Expression; Glucagon-Like Peptide 1 - agonists; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - pharmacology; Glucagon-Like Peptide 1 - physiology; Glucagon-Like Peptide-1 Receptor; In Vitro Techniques; KATP Channels - physiology; Male; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Glucagon - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2008.08.001

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.