{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:06:19Z","timestamp":1788303979986,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Cardiac disease is marked by sympathoexcitation and elevated levels of noradrenaline (NA) and cotransmitter neuropeptide Y (NPY). Increased NPY levels are associated with a greater risk of ventricular arrhythmias and mortality. Nonetheless, the factors that cause NPY release remain poorly understood. We hypothesized that circulating catecholamines might lead to NPY release from myocardial sympathetic nerve terminals via a \u03b2\u2010receptor\u2010mediated mechanism that enhances sympathoexcitation. Ventricular interstitial NA and NPY levels were measured in six Yorkshire pigs after <jats:sc>i.v<\/jats:sc>. administration of NA (1\u00a0mg) and before and after propranolol infusion (1\u00a0mg\/kg). Real\u2010time interstitial NPY levels were measured using ventricular capacitive immunoprobes (CIs) affixed with NPY antibodies and quantified as the change in CI input current (<jats:italic>I<\/jats:italic><jats:sub>NPY<\/jats:sub>) upon binding of NPY. Interstitial NA was measured with adjacent fast\u2010scan cyclic voltammetry probes (<jats:italic>I<\/jats:italic><jats:sub>NA<\/jats:sub>). A left ventricular pressure catheter and continuous ECGs were used for haemodynamic recordings, and an epicardial 56\u2010electrode sock was used for measurements of activation recovery interval, a surrogate of action potential duration. Upon administration of NA, heart rate and left ventricular pressure increased, and activation recovery interval shortened. Notably, NA significantly increased interstitial myocardial NPY levels. After propranolol, changes in heart rate and activation recovery interval were largely mitigated. The <jats:italic>I<\/jats:italic><jats:sub>NA<\/jats:sub> increased to a similar extent post\u2010propranolol <jats:italic>vs<\/jats:italic>. pre\u2010propranolol, but changes in <jats:italic>I<\/jats:italic><jats:sub>NPY<\/jats:sub> were significantly reduced post\u2010propranolol. Coronary sinus plasma analyses confirmed fast\u2010scan cyclic voltammetry and CI findings. Hence, this study demonstrates that circulating NA induces NPY release from ventricular sympathetic nerve terminals, the mechanism for which is mediated via \u03b2\u2010adrenergic receptors and can be blocked by the non\u2010selective \u03b2\u2010blocker, propranolol.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15945-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Cardiovascular disease is characterized by sympathovagal imbalance, with increased plasma noradrenaline (NA) and neuropeptide Y (NPY) concentrations. Increased NPY levels are associated with increased ventricular arrhythmias and mortality in heart failure.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Limited data are available on the specific factors that cause NPY release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this study, fast\u2010scan cyclic voltammetry and capacitive immunoprobes were used to allow for real\u2010time <jats:italic>in vivo<\/jats:italic> measurements of interstitial myocardial neurotransmitters and neuropeptides, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using an <jats:italic>in vivo<\/jats:italic> porcine model with cardiac fast\u2010scan cyclic voltammetry and capacitive immunoprobes, it was shown that systemic NA can increase ventricular interstitial NPY levels, suggesting that NA induces NPY release from postganglionic sympathetic nerves.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The release of NPY was blocked by administration of the non\u2010selective \u03b2\u2010blocker propranolol, suggesting that release of NPY is dependent on activation of \u03b2\u2010adrenergic receptors by NA.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285945","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T08:45:24Z","timestamp":1707900324000},"page":"1911-1921","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Circulating noradrenaline leads to release of neuropeptide Y from cardiac sympathetic nerve terminals via activation of \u03b2\u2010adrenergic receptors"],"prefix":"10.1113","volume":"603","author":[{"given":"Valerie Y. H.","family":"van Weperen","sequence":"first","affiliation":[{"name":"University of California, Los Angeles Cardiac Arrhythmia Center  Los Angeles CA USA"},{"name":"Neurocardiology Research Center of Excellence University of California, Los Angeles  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Hoang","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles Cardiac Arrhythmia Center  Los Angeles CA USA"},{"name":"Neurocardiology Research Center of Excellence University of California, Los Angeles  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Jani","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles Cardiac Arrhythmia Center  Los Angeles CA USA"},{"name":"Neurocardiology Research Center of Excellence University of California, Los Angeles  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artin","family":"Khaky","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles Cardiac Arrhythmia Center  Los Angeles CA USA"},{"name":"Neurocardiology Research Center of Excellence University of California, Los Angeles  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Herring","sequence":"additional","affiliation":[{"name":"Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Case Western Reserve University  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9701-9706","authenticated-orcid":false,"given":"Marmar","family":"Vaseghi","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles Cardiac Arrhythmia Center  Los Angeles CA USA"},{"name":"Neurocardiology Research Center of Excellence University of California, Los Angeles  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1975.tb07328.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01121-4"},{"issue":"3","key":"e_1_2_5_4_1","first-page":"318","article-title":"Coronary sinus neuropeptide Y levels and adverse outcomes in patients with stable chronic heart failure","volume":"5","author":"Ajijola O. 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