Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism.
A lot of interest has engendered in glucagon-like peptide-1 (GLP-1) as an emerging new drug in the treatment of type 2 diabetes. GLP-1 exerts several effects that reduce glycemia in type 2 diabetes patients. We recently also demonstrated that GLP-1 ameliorates endothelial dysfunction in type 2 diabetes mellitus patients with established coronary heart disease, suggesting a new important cardioprotective role for GLP-1. Because hypertension is overrepresented in diabetes and is adversely influencing survival, we have now investigated direct GLP-1 effects on vascular beds in a rat organ bath model. It was found that GLP-1 relaxed femoral artery rings in a dose-response manner. The relaxant effect from GLP-1 was completely inhibited by the specific GLP-1 receptor antagonist, exendin(9-39). Neither the specific nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine, nor removing of endothelium, affected the GLP-1 relaxant effect. In conclusion, we now report a direct vascular action of GLP-1, relaxing conduit vessels independently of NO and the endothelium.
Nyström
Thomas
T
Karolinska Institutet, Department of Internal Medicine, Stockholm South Hospital SE-118 83 Stockholm, Sweden. thomas.nystrom@sos.sll.se
Gonon
Adrian T
AT
Sjöholm
Ake
A
Pernow
John
J
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005263:Femoral Artery / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000378:metabolism
D002316:Cardiotonic Agents; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D019335:Nitroarginine; D009569:Nitric Oxide; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D011188:Potassium