Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism
Abstract
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.
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Nitric oxide mediates some effects of GLP-1, including inhibition of small bowel motility in rats, protection against ethanol-induced gastric mucosal lesions, and relaxation of vascular endothelium.
“Because nitric oxide (NO) mediates some effects of GLP-1 (e.g., inhibition of small bowel motility in rats) (48)—protection against ethanol-induced gastric mucosal lesions (20) and relaxation of vascular endothelium (31)]”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [31]
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- Authors
- Nyström, T., Gonon, A. T., Sjöholm, Å., & Pernow, J.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Nyström, Thomas
- Venue
- Regulatory Peptides
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 125
- Issue
- 1-3
- Pages
- 173-177
- ISSN
- 0167-0115 (ISSN-L)
- OpenAlex
- W2005140805
- Cited by
- 188
- References
- 22
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 9 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 18 · 2014: 17 · 2013: 11 · 2012: 26
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regulatory Peptides (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucagon-like peptide-1, conduit arteries, vasorelaxation, nitric oxide, exendin-9-39, GLP-1 receptor, type 2 diabetes, hypertension, femoral artery, cardioprotection
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Acetylcholine, Cyclic AMP, Animals, Arteries, Cardiotonic Agents, Dose-Response Relationship, Drug, Endothelium, Vascular, Femoral Artery, Glucagon, Male, Nitric Oxide, Peptide Fragments, Potassium, Protein Precursors, Rats, Sprague-Dawley, Receptors, Glucagon, Nitric Oxide Synthase, Nitroarginine, Rats, Glucagon-Like Peptide 1
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