ArticleNature medicine2013
GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
248 citing papers in PubMed, 3 syntheses or guidelines pooled it, 494 citations in OpenAlex.
- Influence of glucagon-like peptide-1 receptor agonists on renal parameters: a meta-analysis of randomized controlled trials.BMC endocrine disorders · 2025Pooled it
- A Review and Meta-Analysis of the Safety and Efficacy of Using Glucagon-like Peptide-1 Receptor Agonists.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Effect of Hemoglobin A1c Reduction or Weight Reduction on Blood Pressure in Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Treatment in Type 2 Diabetes Mellitus: A Meta-Analysis.Journal of the American Heart Association · 2020Pooled it
- GLP-1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading.Journal of the American Heart Association · 2023Trial
- The renoprotective effect and safety of a DPP-4 inhibitor, sitagliptin, at a small dose in type 2 diabetic patients with a renal dysfunction when changed from other DPP-4 inhibitors: REAL trial.Clinical and experimental nephrology · 2018Trial
- Glucagon-Like Peptide-1 Agonists and Blood Pressure Regulation: Molecular Mechanisms and Cardiovascular Implications.Pharmacology research & perspectives · 2026Review
- Future GLP-1 receptor co-agonists and their cardiac effects.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Contractile effects of dulaglutide in the human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A clinical and experimental investigation of liraglutide effects on the brain-kidney axis.Science advances · 2026Article
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Hemodynamic and metabolomic responses to infusion of GLP-1 agonist exenatide in pulmonary arterial hypertension.JCI insight · 2026Article
- Differential effects of semaglutide and colchicine on atrial remodeling in rats with reduced ejection fraction after myocardial infarction.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Roflumilast Enhances Liraglutide's Atrial Natriuretic Peptide-Dependent Suppression of Adrenal Aldosterone Secretion.International journal of molecular sciences · 2026Article
- GLP-1 Receptor Agonists and Blood Pressure: A State-of-the-Art Review of Mechanisms, Evidence, and Clinical Implications.American journal of hypertension · 2026Review
- Mechanisms of GLP-1 Receptor Agonists in HFpEF: Exploring Weight-Dependent and Independent Drivers of Therapeutic Benefit.Circulation. Heart failure · 2026Review
- Exploring the therapeutic potential of GLP-1 receptor agonists in pulmonary arterial hypertension.ERJ open research · 2026Review
- Semaglutide reduces murine blood pressure through the vascular smooth muscle GLP-1 receptor.JCI insight · 2026Article
- Acute Contractile Effects of Glucagon-like-Peptide-1 Receptor Agonists in the Human Heart.Pharmaceutics · 2026Review
- Integrating GLP-1 Receptor Agonists into Modern Stroke Prevention: Evidence, Mechanisms, and Clinical Consideration-A Narrative Review.Biomedicines · 2026Review
- GLP-1 and the cardiovascular system.The Journal of clinical investigation · 2026Review
188 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) agonists exert antihypertensive actions through incompletely understood mechanisms. Here we demonstrate that cardiac Glp1r expression is localized to cardiac atria and that GLP-1R activation promotes the secretion of atrial natriuretic peptide (ANP) and a reduction of blood pressure. Consistent with an indirect ANP-dependent mechanism for the antihypertensive effects of GLP-1R activation, the GLP-1R agonist liraglutide did not directly increase the amount of cyclic GMP (cGMP) or relax preconstricted aortic rings; however, conditioned medium from liraglutide-treated hearts relaxed aortic rings in an endothelium-independent, GLP-1R-dependent manner. Liraglutide did not induce ANP secretion, vasorelaxation or lower blood pressure in Glp1r(-/-) or Nppa(-/-) mice. Cardiomyocyte GLP-1R activation promoted the translocation of the Rap guanine nucleotide exchange factor Epac2 (also known as Rapgef4) to the membrane, whereas Epac2 deficiency eliminated GLP-1R-dependent stimulation of ANP secretion. Plasma ANP concentrations were increased after refeeding in wild-type but not Glp1r(-/-) mice, and liraglutide increased urine sodium excretion in wild-type but not Nppa(-/-) mice. These findings define a gut-heart GLP-1R-dependent and ANP-dependent axis that regulates blood pressure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.