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

Arch Biochem Biophys. 2008 Oct 15;478(2):136-42. doi: 10.1016/ Epub 2008 Aug 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • DNA Primers
  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • KATP Channels
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Glucagon
  • glucagon-like peptide 1 (7-36)amide
  • exendin (9-39)
  • Glucagon-Like Peptide 1
  • Cyclic AMP