{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T21:47:20Z","timestamp":1766267240117},"reference-count":42,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:p>The hormone ghrelin prevents a dangerous increase in cardiac sympathetic nerve activity (SNA) after acute myocardial infarction (MI), although the underlying mechanisms remain unknown. This study aimed to determine whether ghrelin's sympathoinhibitory properties stem either from directly within the central nervous system, or via modulation of specific cardiac vagal inhibitory afferents. Cardiac SNA was recorded in urethane-anesthetized rats for 3 hours after the ligation of the left anterior descending coronary artery (ie, MI). Rats received ghrelin either sc (150 \u03bcg\/kg) or intracerebroventricularly (5 \u03bcg\/kg) immediately after the MI. In another two groups, the cervical vagi were denervated prior to the MI, followed by sc injection of either ghrelin or placebo. Acute MI induced a 188% increase in cardiac SNA, which was significantly attenuated in ghrelin-treated rats for both sc or intracerebroventricularly administration (36% and 76% increase, respectively). Consequently, mortality (47%) and the incidence of arrhythmic episodes (12 per 2 h) were improved with both routes of ghrelin administration (&amp;lt;13% and less than five per 2 h, respectively). Bilateral vagotomy significantly attenuated the cardiac SNA response to acute MI (99% increase). Ghrelin further attenuated the sympathetic response to MI in vagotomized rats so that the SNA response was comparable between vagotomized and vagal-intact MI rats treated with ghrelin. These results suggest that ghrelin may act primarily via a central pathway within the brain to suppress SNA after MI, although peripheral vagal afferent pathways may also contribute in part. The exact region(s) within the central nervous system whereby ghrelin inhibits SNA remains to be fully elucidated.<\/jats:p>","DOI":"10.1210\/en.2015-1333","type":"journal-article","created":{"date-parts":[[2015,6,29]],"date-time":"2015-06-29T17:30:31Z","timestamp":1435599031000},"page":"3309-3316","source":"Crossref","is-referenced-by-count":19,"title":["Ghrelin Supresses Sympathetic Hyperexcitation in Acute Heart Failure in Male Rats: Assessing Centrally and Peripherally Mediated Pathways"],"prefix":"10.1210","volume":"156","author":[{"given":"Mikiyasu","family":"Shirai","sequence":"first","affiliation":[{"name":"Department of Cardiac Physiology (M.S., H.T., T.S.), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Joe","sequence":"first","affiliation":[{"name":"Department of Physiology-Heart Otago (N.J., D.O.S.), University of Otago, Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotsugu","family":"Tsuchimochi","sequence":"first","affiliation":[{"name":"Department of Cardiac Physiology (M.S., H.T., T.S.), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Sonobe","sequence":"first","affiliation":[{"name":"Department of Cardiac Physiology (M.S., H.T., T.S.), National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryl O.","family":"Schwenke","sequence":"first","affiliation":[{"name":"Department of Physiology-Heart Otago (N.J., D.O.S.), University of Otago, Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2015,6,29]]},"reference":[{"key":"2020071612115236200_B1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1113\/jphysiol.2004.082198","article-title":"Increased cardiac sympathetic nerve activity following acute myocardial infarction in a sheep model","volume":"565","author":"Jardine","year":"2005","journal-title":"J Physiol"},{"key":"2020071612115236200_B2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11897-009-0013-9","article-title":"The brain renin-angiotensin-aldosterone system: a major mechanism for sympathetic hyperactivity and left ventricular remodeling and dysfunction after myocardial infarction","volume":"6","author":"Huang","year":"2009","journal-title":"Curr Heart Fail Rep"},{"key":"2020071612115236200_B3","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.2967\/jnumed.107.043794","article-title":"Decreased myocardial \u03b2-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy","volume":"48","author":"Tsukamoto","year":"2007","journal-title":"J Nucl Med"},{"key":"2020071612115236200_B4","doi-asserted-by":"crossref","first-page":"16378","DOI":"10.1074\/jbc.M109.077859","article-title":"Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction","volume":"285","author":"Lymperopoulos","year":"2010","journal-title":"J Biol Chem"},{"key":"2020071612115236200_B5","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1210\/en.2011-2057","article-title":"One dose of ghrelin prevents the acute and sustained increase in cardiac sympathetic tone after myocardial infarction","volume":"153","author":"Schwenke","year":"2012","journal-title":"Endocrinology"},{"key":"2020071612115236200_B6","doi-asserted-by":"crossref","first-page":"5172","DOI":"10.1210\/en.2008-0472","article-title":"Early ghrelin treatment after myocardial infarction prevents an increase in cardiac sympathetic tone and reduces mortality","volume":"149","author":"Schwenke","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612115236200_B7","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature"},{"key":"2020071612115236200_B8","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1523\/JNEUROSCI.3218-05.2006","article-title":"The subfornical organ: a central target for circulating feeding signals","volume":"26","author":"Pulman","year":"2006","journal-title":"J Neurosci"},{"key":"2020071612115236200_B9","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1161\/01.HYP.0000122803.91559.55","article-title":"Ghrelin acts at the nucleus of the solitary tract to decrease arterial pressure in rats","volume":"43","author":"Lin","year":"2004","journal-title":"Hypertension"},{"key":"2020071612115236200_B10","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1161\/01.HYP.0000035395.51441.10","article-title":"Central ghrelin modulates sympathetic activity in conscious rabbits","volume":"40","author":"Matsumura","year":"2002","journal-title":"Hypertension"},{"key":"2020071612115236200_B11","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1053\/gast.2002.35954","article-title":"The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats","volume":"123","author":"Date","year":"2002","journal-title":"Gastroenterology"},{"key":"2020071612115236200_B12","doi-asserted-by":"crossref","first-page":"H426","DOI":"10.1152\/ajpheart.00643.2007","article-title":"Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction","volume":"294","author":"Soeki","year":"2008","journal-title":"Am J Physiol (Heart Circ Physiol)"},{"key":"2020071612115236200_B13","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1210\/en.2012-1065","article-title":"Ghrelin prevents incidence of malignant arrhythmia after acute myocardial infarction through vagal afferent nerves","volume":"153","author":"Mao","year":"2012","journal-title":"Endocrinology"},{"key":"2020071612115236200_B14","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1365-2265.2010.03865.x","article-title":"Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects","volume":"73","author":"Huda","year":"2010","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071612115236200_B15","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1007\/s00395-014-0432-y","article-title":"Pulmonary vascular tone is dependent on the central modulation of sympathetic nerve activity following chronic intermittent hypoxia","volume":"109","author":"Shirai","year":"2014","journal-title":"Basic Res Cardiol"},{"key":"2020071612115236200_B16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1161\/HYPERTENSIONAHA.111.171025","article-title":"Ghrelin modulates sympathetic nervous system activity and stress response in lean and overweight men","volume":"58","author":"Lambert","year":"2011","journal-title":"Hypertension"},{"key":"2020071612115236200_B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.peptides.2014.09.015","article-title":"Effect of ghrelin on autonomic activity in healthy volunteers","volume":"62C","author":"Soeki","year":"2014","journal-title":"Peptides"},{"key":"2020071612115236200_B18","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1210\/en.2012-2132","article-title":"Excessive sympathoactivation and deteriorated heart function after myocardial infarction in male ghrelin knockout mice","volume":"154","author":"Mao","year":"2013","journal-title":"Endocrinology"},{"key":"2020071612115236200_B19","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1111\/j.1440-1681.2006.04523.x","article-title":"Mechanisms of sympathetic activation in heart failure","volume":"33","author":"Watson","year":"2006","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2020071612115236200_B20","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jacc.2011.11.031","article-title":"Neural remodeling and myocardial infarction: the stellate ganglion as a double agent","volume":"59","author":"Ajijola","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"2020071612115236200_B21","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/01.RES.49.1.159","article-title":"The influence of vagal afferents on the left ventricular contractile response to intracoronary administration of catecholamines in the conscious dog","volume":"49","author":"Barron","year":"1981","journal-title":"Circ Res"},{"key":"2020071612115236200_B22","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.autneu.2008.05.001","article-title":"Reflex control of sympathetic outflow and depressed baroreflex sensitivity following myocardial infarction","volume":"141","author":"Jones","year":"2008","journal-title":"Auton Neurosci"},{"key":"2020071612115236200_B23","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/0002-9149(74)90632-8","article-title":"Reflex inhibitory effects of vagal afferents in experimental myocardial infarction","volume":"33","author":"Kezdi","year":"1974","journal-title":"Am J Cardiol"},{"key":"2020071612115236200_B24","doi-asserted-by":"crossref","first-page":"H791","DOI":"10.1152\/ajpheart.00099.2004","article-title":"Neural regulation of the proinflammatory cytokine response to acute myocardial infarction","volume":"287","author":"Francis","year":"2004","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2020071612115236200_B25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1113\/jphysiol.2012.236059","article-title":"The role of the paraventricular nucleus of the hypothalamus in the regulation of cardiac and renal sympathetic nerve activity in conscious normal and heart failure sheep","volume":"591","author":"Ramchandra","year":"2013","journal-title":"J Physiol"},{"key":"2020071612115236200_B26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0006-8993(00)02186-7","article-title":"Neuronal expression of Fos protein in the hypothalamus of rats with heart failure","volume":"865","author":"Patel","year":"2000","journal-title":"Brain Res"},{"key":"2020071612115236200_B27","first-page":"191","article-title":"Influence of parasympathetic pathways on early post-infarction arrhythmias","volume":"22","author":"Garcia-Perez","year":"1980","journal-title":"Cor Vasa"},{"key":"2020071612115236200_B28","first-page":"379","article-title":"Influence of vagal suppression on early arrhythmias following experimental myocardial infarction in dogs","volume":"20","author":"Nieto Lluis","year":"1978","journal-title":"Cor Vasa"},{"key":"2020071612115236200_B29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.peptides.2013.02.003","article-title":"Chronic central ghrelin infusion reduces blood pressure and heart rate despite increasing appetite and promoting weight gain in normotensive and hypertensive rats","volume":"42","author":"Freeman","year":"2013","journal-title":"Peptides"},{"key":"2020071612115236200_B30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.autneu.2011.04.001","article-title":"Centrally administered ghrelin activates cardiac vagal nerve in anesthetized rabbits","volume":"162","author":"Shimizu","year":"2011","journal-title":"Auton Neurosci"},{"key":"2020071612115236200_B31","doi-asserted-by":"crossref","first-page":"R217","DOI":"10.1152\/ajpregu.00878.2007","article-title":"Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat","volume":"296","author":"Kobashi","year":"2009","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2020071612115236200_B32","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ijcard.2006.09.016","article-title":"Myocardial ischemia and ventricular fibrillation: pathophysiology and clinical implications","volume":"119","author":"Luqman","year":"2007","journal-title":"Int J Cardiol"},{"key":"2020071612115236200_B33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1053\/eupc.2000.0136","article-title":"Limitations of the use of spectral analysis of heart rate variability for the estimation of cardiac sympathetic activity in heart failure","volume":"3","author":"Notarius","year":"2001","journal-title":"Europace"},{"key":"2020071612115236200_B34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0002-9149(94)90421-9","article-title":"Limitations of heart rate variability measurements","volume":"74","author":"Sanderson","year":"1994","journal-title":"Am J Cardiol"},{"key":"2020071612115236200_B35","doi-asserted-by":"crossref","first-page":"R683","DOI":"10.1152\/ajpregu.2001.281.3.R683","article-title":"Differential control of sympathetic outflow","volume":"281","author":"Morrison","year":"2001","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2020071612115236200_B36","doi-asserted-by":"crossref","first-page":"R1230","DOI":"10.1152\/ajpregu.00713.2010","article-title":"Differential activation of adrenal, renal, and lumbar sympathetic nerves following stimulation of the rostral ventrolateral medulla of the rat","volume":"300","author":"Mueller","year":"2011","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2020071612115236200_B37","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/jne.12168","article-title":"Divergent neuronal circuitries underlying acute orexigenic effects of peripheral or central ghrelin: critical role of brain accessibility","volume":"26","author":"Cabral","year":"2014","journal-title":"J Neuroendocrinol"},{"key":"2020071612115236200_B38","doi-asserted-by":"crossref","first-page":"H1011","DOI":"10.1152\/ajpheart.00418.2012","article-title":"Sites of action of ghrelin receptor ligands in cardiovascular control","volume":"303","author":"Callaghan","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2020071612115236200_B39","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/cne.20823","article-title":"Expression of ghrelin receptor mRNA in the rat and the mouse brain","volume":"494","author":"Zigman","year":"2006","journal-title":"J Comp Neurol"},{"key":"2020071612115236200_B40","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1002\/cne.23309","article-title":"Expression of the ghrelin receptor gene in neurons of the medulla oblongata of the rat","volume":"521","author":"Bron","year":"2013","journal-title":"J Comp Neurol"},{"key":"2020071612115236200_B41","first-page":"63","volume-title":"Peptidergic Control of Oxytocin and Vasopressin Neurons and Its Role in Reproductive and Hypertension-Associated Plasticity. Neurophysiology of Neuroendocrine Neurons","author":"Brown","year":"2014"},{"key":"2020071612115236200_B42","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0165-1838(98)00084-8","article-title":"Differential effects of anesthetics on sympathetic nerve activity and arterial baroreceptor reflex in chronically instrumented rats","volume":"72","author":"Shimokawa","year":"1998","journal-title":"J Auton Nerv Syst"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/156\/9\/3309\/8995395\/endo3309.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/156\/9\/3309\/8995395\/endo3309.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T19:28:39Z","timestamp":1594927719000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/156\/9\/3309\/2422995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,29]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2015-1333","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,29]]}}}