GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta through a pathway involving KATP and cAMP.
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.
Green
Brian D
BD
Human Nutrition & Health Group, School of Biological Sciences, Queens University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK. b.green@qub.ac.uk
Hand
Katharine V
KV
Dougan
Janette E
JE
McDonnell
Bronagh M
BM
Cassidy
Roslyn S
RS
Grieve
David J
DJ
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D000067757:Glucagon-Like Peptide-1 Receptor; D066298:In Vitro Techniques; D054086:KATP Channels / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D017931:DNA Primers; C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D054086:KATP Channels; D010446:Peptide Fragments; D012333:RNA, Messenger; D018027:Receptors, Glucagon; C055453:glucagon-like peptide 1 (7-36)amide; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP