{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:08:43Z","timestamp":1789006123607,"version":"build-2803163510"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular outcomes in patients with type 2 diabetes mellitus. However, systemic actions of these agents cause sympathetic activation, which is generally considered to be detrimental in cardiovascular disease. Despite significant research interest in cardiovascular biology of GLP-1, the presence of GLP-1R in ventricular cardiomyocytes remains a controversial issue, and the effects of this peptide on the electrical properties of intact ventricular myocardium are unknown. We sought to determine the effects of GLP-1R agonist exendin-4 (Ex4) on ventricular action potential duration (APD) and susceptibility to ventricular arrhythmia in the rat heart in vivo and ex vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Ventricular monophasic action potentials were recorded in anaesthetized (urethane) rats in vivo and isolated perfused rat hearts during sinus rhythm and ventricular pacing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In vivo, systemic administration of Ex4 (5 \u03bcg\/kg intravenously) increased heart rate, and this effect was abolished by \u03b2-adrenoceptor blockade. Despite causing sympathetic activation, Ex4 increased APD at 90% repolarization during ventricular pacing by 7% (\n                      <jats:italic>P<\/jats:italic>\n                      =0.044; n=6) and reversed the effect of \u03b2-adrenoceptor agonist dobutamine on APD at 90% repolarization. In isolated perfused hearts, Ex4 (3 nmol\/L) increased APD at 90% repolarization by 14% (\n                      <jats:italic>P<\/jats:italic>\n                      =0.015; n=6) with no effect on heart rate. Ex4 also reduced ventricular arrhythmia inducibility in conditions of \u03b2-adrenoceptor stimulation with isoproterenol. Ex4 effects on APD and ventricular arrhythmia susceptibility were prevented in conditions of muscarinic receptor blockade or inhibition of nitric oxide synthase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>These data demonstrate that GLP-1R activation effectively opposes the effects of \u03b2-adrenoceptor stimulation on cardiac ventricular excitability and reduces ventricular arrhythmic potential. The effect of GLP-1R activation on the ventricular myocardium is indirect, mediated by acetylcholine and nitric oxide and, therefore, can be explained by stimulation of cardiac parasympathetic (vagal) neurons.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circep.118.006740","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T05:00:24Z","timestamp":1539234024000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Modulation of Cardiac Ventricular Excitability by GLP-1 (Glucagon-Like Peptide-1)"],"prefix":"10.1161","volume":"11","author":[{"given":"Richard","family":"Ang","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology &amp; Pharmacology, University College London, United Kingdom (R.A., S.M., P.S.H., M.B., A.V.G.)"},{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (R.A., M.S., Q.A., Y.L., A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Mastitskaya","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology &amp; Pharmacology, University College London, United Kingdom (R.A., S.M., P.S.H., M.B., A.V.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Hosford","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology &amp; Pharmacology, University College London, United Kingdom (R.A., S.M., P.S.H., M.B., A.V.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Basalay","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology &amp; Pharmacology, University College London, United Kingdom (R.A., S.M., P.S.H., M.B., A.V.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Specterman","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (R.A., M.S., Q.A., Y.L., A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qadeer","family":"Aziz","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (R.A., M.S., Q.A., Y.L., A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Li","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (R.A., M.S., Q.A., Y.L., A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Orini","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, University College London, United Kingdom (M.O., P.T., P.D.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Taggart","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, University College London, United Kingdom (M.O., P.T., P.D.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier D.","family":"Lambiase","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, University College London, United Kingdom (M.O., P.T., P.D.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Gourine","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Karolinska Institute, Stockholm, Sweden (A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Tinker","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (R.A., M.S., Q.A., Y.L., A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Gourine","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology &amp; 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