{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:33:21Z","timestamp":1786980801322,"version":"build-2736575974"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T00:00:00Z","timestamp":1611360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T00:00:00Z","timestamp":1611360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011660","name":"European Association of Cardiothoracic Anaesthesiology","doi-asserted-by":"publisher","award":["Research Grant 2016"],"award-info":[{"award-number":["Research Grant 2016"]}],"id":[{"id":"10.13039\/501100011660","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007534","name":"B. Braun Melsungen","doi-asserted-by":"publisher","award":["BBST-D-14-00037"],"award-info":[{"award-number":["BBST-D-14-00037"]}],"id":[{"id":"10.13039\/100007534","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Drugs Ther"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation\u2013contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Volume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095 rats each), hemodynamic and humoral parameters were assessed 28\u00a0days after ACF induction. Sham-operated animals served as controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10557-020-07132-4","type":"journal-article","created":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T02:03:23Z","timestamp":1611367403000},"page":"733-743","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats"],"prefix":"10.1007","volume":"35","author":[{"given":"Lukas","family":"Dehe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Shaqura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nordine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Habazettl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"von Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Schluchter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Shakibaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaaban A.","family":"Mousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00e4fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-7680","authenticated-orcid":false,"given":"Sascha","family":"Treskatsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,23]]},"reference":[{"key":"7132_CR1","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","volume":"37","author":"P Ponikowski","year":"2016","unstructured":"Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129\u2013200.","journal-title":"Eur Heart J"},{"key":"7132_CR2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0140-6736(12)61148-9","volume":"380","author":"RM Pearse","year":"2012","unstructured":"Pearse RM, Moreno RP, Bauer P, Pelosi P, Metnitz P, Spies C, et al. Mortality after surgery in Europe: a 7 day cohort study. Lancet. 2012;380:1059\u201365.","journal-title":"Lancet."},{"key":"7132_CR3","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1111\/bph.13042","volume":"172","author":"JP Headrick","year":"2015","unstructured":"Headrick JP, See Hoe LE, Toit Du EF, Peart JN. Opioid receptors and cardioprotection - \u201copioidergic conditioning\u201d of the heart. Br J Pharmacol. 2015;172:2026\u201350.","journal-title":"Br J Pharmacol"},{"key":"7132_CR4","doi-asserted-by":"crossref","unstructured":"Goudra BG, Duggan M, Chidambaran V, et al. Anesthesiology. 1st ed: Springer; 2018.","DOI":"10.1007\/978-3-319-74766-8"},{"key":"7132_CR5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00380-014-0620-6","volume":"31","author":"S Treskatsch","year":"2015","unstructured":"Treskatsch S, Feldheiser A, Shaqura M, et al. Cellular localization and adaptive changes of the cardiac delta opioid receptor system in an experimental model of heart failure in rats. Heart Vessel. 2015;31:241\u201350.","journal-title":"Heart Vessel"},{"key":"7132_CR6","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1007\/s00380-015-0784-8","volume":"31","author":"S Treskatsch","year":"2015","unstructured":"Treskatsch S, Shaqura M, Dehe L, et al. Evidence for MOR on cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular myocardium in rats. Heart Vessel. 2015;31:1380\u20138.","journal-title":"Heart Vessel"},{"key":"7132_CR7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.phrs.2015.09.005","volume":"102","author":"S Treskatsch","year":"2015","unstructured":"Treskatsch S, Shaqura M, Dehe L, Feldheiser A, Roepke TK, Shakibaei M, et al. Upregulation of the kappa opioidergic system in left ventricular rat myocardium in response to volume overload: adaptive changes of the cardiac kappa opioid system in heart failure. Pharmacol Res. 2015;102:33\u201341.","journal-title":"Pharmacol Res"},{"key":"7132_CR8","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00380-013-0456-5","volume":"29","author":"P Sobanski","year":"2014","unstructured":"Sobanski P, Krajnik M, Shaqura M, Bloch-Boguslawska E, Sch\u00e4fer M, Mousa SA. The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue. Heart Vessel. 2014;29:855\u201363.","journal-title":"Heart Vessel"},{"key":"7132_CR9","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/cne.22560","volume":"519","author":"SA Mousa","year":"2011","unstructured":"Mousa SA, Shaqura M, Sch\u00e4per J, Treskatsch S, Habazettl H, Sch\u00e4fer M, et al. Developmental expression of \u03b4-opioid receptors during maturation of the parasympathetic, sympathetic, and sensory innervations of the neonatal heart: early targets for opioid regulation of autonomic control. J Comp Neurol. 2011;519:957\u201371.","journal-title":"J Comp Neurol"},{"key":"7132_CR10","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1002\/cne.22427","volume":"518","author":"SA Mousa","year":"2010","unstructured":"Mousa SA, Shaqura M, Sch\u00e4per J, Huang W, Treskatsch S, Habazettl H, et al. Identification of mu- and kappa-opioid receptors as potential targets to regulate parasympathetic, sympathetic, and sensory neurons within rat intracardiac ganglia. J Comp Neurol. 2010;518:3836\u201347.","journal-title":"J Comp Neurol"},{"key":"7132_CR11","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.yjmcc.2009.06.016","volume":"47","author":"C Bolte","year":"2009","unstructured":"Bolte C, Newman G, Schultz JEJ. Kappa and delta opioid receptor signaling is augmented in the failing heart. J Mol Cell Cardiol. 2009;47:493\u2013503.","journal-title":"J Mol Cell Cardiol"},{"key":"7132_CR12","first-page":"H912","volume":"267","author":"N Imai","year":"1994","unstructured":"Imai N, Kashiki M, Woolf PD, Liang CS. Comparison of cardiovascular effects of mu- and delta-opioid receptor antagonists in dogs with congestive heart failure. Am J Phys. 1994;267:H912\u20137.","journal-title":"Am J Phys"},{"key":"7132_CR13","doi-asserted-by":"crossref","first-page":"e87531","DOI":"10.1371\/journal.pone.0087531","volume":"9","author":"S Treskatsch","year":"2014","unstructured":"Treskatsch S, Feldheiser A, Rosin AT, Sifringer M, Habazettl H, Mousa SA, et al. A modified approach to induce predictable congestive heart failure by volume overload in rats. PLoS One. 2014;9:e87531\u20137.","journal-title":"PLoS One"},{"key":"7132_CR14","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10495-009-0441-8","volume":"15","author":"MR Dent","year":"2010","unstructured":"Dent MR, Tappia PS, Dhalla NS. Gender differences in apoptotic signaling in heart failure due to volume overload. Apoptosis. 2010;15:499\u2013510.","journal-title":"Apoptosis."},{"key":"7132_CR15","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/j.1530-0277.2009.01090.x","volume":"34","author":"KG Hill","year":"2010","unstructured":"Hill KG, Sable HJK, Ferraro FM, Kiefer SW. Chronic naltrexone treatment and ethanol responsivity in outbred rats. Alcohol Clin Exp Res. 2010;34:272\u20139.","journal-title":"Alcohol Clin Exp Res"},{"key":"7132_CR16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1177\/2042098617744161","volume":"9","author":"R Rzasa Lynn","year":"2018","unstructured":"Rzasa Lynn R, Galinkin JL. Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf. 2018;9:63\u201388.","journal-title":"Ther Adv Drug Saf"},{"key":"7132_CR17","first-page":"273","volume":"3","author":"BL Crabtree","year":"1984","unstructured":"Crabtree BL. Review of naltrexone, a long-acting opiate antagonist. Clin Pharm. 1984;3:273\u201380.","journal-title":"Clin Pharm"},{"key":"7132_CR18","first-page":"74","volume":"46","author":"DC Saha","year":"2007","unstructured":"Saha DC, Saha AC, Malik G, Astiz ME, Rackow EC. Comparison of cardiovascular effects of tiletamine-zolazepam, pentobarbital, and ketamine-xylazine in male rats. J Am Assoc Lab Anim Sci. 2007;46:74\u201380.","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"7132_CR19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1353\/pbm.1967.0031","volume":"10","author":"IH Page","year":"1967","unstructured":"Page IH. The mosaic theory of arterial hypertension - its interpretation. Perspect Biol Med. 1967;10:325\u201333.","journal-title":"Perspect Biol Med"},{"key":"7132_CR20","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1161\/CIRCRESAHA.107.166033","volume":"102","author":"FM Heidrich","year":"2008","unstructured":"Heidrich FM, Zhang K, Estrada M, Huang Y, Giordano FJ, Ehrlich BE. Chromogranin B regulates calcium signaling, nuclear factor kappaB activity, and brain natriuretic peptide production in cardiomyocytes. Circ Res. 2008;102:1230\u20138.","journal-title":"Circ Res"},{"key":"7132_CR21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/0306-4522(95)00464-5","volume":"71","author":"A Mansour","year":"1996","unstructured":"Mansour A, Burke S, Pavlic RJ, Akil H, Watson SJ. Immunohistochemical localization of the cloned kappa 1 receptor in the rat CNS and pituitary. Neuroscience. 1996;71:671\u201390.","journal-title":"Neuroscience."},{"key":"7132_CR22","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/0896-6273(89)90196-7","volume":"2","author":"ME Morton","year":"1989","unstructured":"Morton ME, Froehner SC. The alpha 1 and alpha 2 polypeptides of the dihydropyridine-sensitive calcium channel differ in developmental expression and tissue distribution. Neuron. 1989;2:1499\u2013506.","journal-title":"Neuron."},{"key":"7132_CR23","doi-asserted-by":"crossref","first-page":"7500","DOI":"10.1073\/pnas.0503465103","volume":"103","author":"RC Balijepalli","year":"2006","unstructured":"Balijepalli RC, Foell JD, Hall DD, Hell JW, Kamp TJ. Localization of cardiac L-type Ca (2+) channels to a caveolar macromolecular signaling complex is required for beta (2)-adrenergic regulation. Proc Natl Acad Sci. 2006;103:7500\u20135.","journal-title":"Proc Natl Acad Sci"},{"key":"7132_CR24","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101\u20138.","journal-title":"Nat Protoc"},{"key":"7132_CR25","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s00259-002-0897-z","volume":"29","author":"PSR Villemagne","year":"2002","unstructured":"Villemagne PSR, Dannals RF, Ravert HT, Frost JJ. PET imaging of human cardiac opioid receptors. Eur J Nucl Med Mol Imaging. 2002;29:1385\u20138.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7132_CR26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.ijcard.2015.06.067","volume":"197","author":"S Treskatsch","year":"2015","unstructured":"Treskatsch S, Shakibaei M, Feldheiser A, Shaqura M, Dehe L, Roepke TK, et al. Ultrastructural changes associated with myocardial apoptosis, in failing rat hearts induced by volume overload. Int J Cardiol. 2015;197:327\u201332.","journal-title":"Int J Cardiol"},{"key":"7132_CR27","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S0006-8993(99)02432-4","volume":"857","author":"A Ros\u00e9n","year":"2000","unstructured":"Ros\u00e9n A, Lundeberg T, Bytner B, Nylander I. Central changes in nociceptin dynorphin B and Met-enkephalin-Arg-Phe in different models of nociception. Brain Res. 2000;857:212\u20138.","journal-title":"Brain Res"},{"key":"7132_CR28","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0006-8993(95)01434-9","volume":"709","author":"PD Feldman","year":"1996","unstructured":"Feldman PD, Parveen N, Sezen S. Cardiovascular effects of Leu-enkephalin in the nucleus tractus solitarius of the rat. Brain Res. 1996;709:331\u20136.","journal-title":"Brain Res"},{"key":"7132_CR29","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1097\/00000542-198411000-00004","volume":"61","author":"JG Bovill","year":"1984","unstructured":"Bovill JG, Sebel PS, Stanley TH. Opioid analgesics in anesthesia: with special reference to their use in cardiovascular anesthesia. Anesthesiology. 1984;61:731\u201355.","journal-title":"Anesthesiology."},{"key":"7132_CR30","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/164_2017_6","volume":"247","author":"L See Hoe","year":"2018","unstructured":"See Hoe L, Patel HH, Peart JN. Delta opioid receptors and cardioprotection. Handb Exp Pharmacol. 2018;247:301\u201334.","journal-title":"Handb Exp Pharmacol"},{"key":"7132_CR31","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.ahj.2005.02.010","volume":"149","author":"TJ Meine","year":"2005","unstructured":"Meine TJ, Roe MT, Chen AY, Patel MR, Washam JB, Ohman EM, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE quality improvement initiative. Am Heart J. 2005;149:1043\u20139.","journal-title":"Am Heart J"},{"key":"7132_CR32","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.ahj.2004.01.029","volume":"148","author":"D Cozzolino","year":"2004","unstructured":"Cozzolino D, Sasso FC, Salvatore T, Torella M, Cittadini A, Gentile S, et al. Acute effects of \u03b2-endorphin on cardiovascular function in patients with mild to moderate chronic heart failure. Am Heart J. 2004;148:530\u20137.","journal-title":"Am Heart J"},{"key":"7132_CR33","first-page":"189","volume":"23","author":"T Vargish","year":"1987","unstructured":"Vargish T, Beamer KC, Daly T, Riggs TR. Morphine sulfate depression of cardiac function is attenuated by opiate receptor antagonism with naloxone. Circ Shock. 1987;23:189\u201395.","journal-title":"Circ Shock"},{"key":"7132_CR34","first-page":"H478","volume":"272","author":"A Yatani","year":"1997","unstructured":"Yatani A, Imai N, Himura Y, Suematsu M, Liang CS. Chronic opiate-receptor inhibition in experimental congestive heart failure in dogs. Am J Phys. 1997;272:H478\u201384.","journal-title":"Am J Phys"},{"key":"7132_CR35","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cardiores.2004.04.022","volume":"63","author":"S Pepe","year":"2004","unstructured":"Pepe S. Cross-talk of opioid peptide receptor and \u00df-adrenergic receptor signalling in the heart. Cardiovasc Res. 2004;63:414\u201322.","journal-title":"Cardiovasc Res"},{"key":"7132_CR36","first-page":"1305","volume":"21","author":"M Yeganeh-Hajahmadi","year":"2018","unstructured":"Yeganeh-Hajahmadi M, Najafipour H, Farzaneh F, Esmaeili-Mahani S, Joukar S. Effect of apelin on cardiac contractility in acute reno-vascular hypertension: the role of apelin receptor and kappa opioid receptor heterodimerization. Iran J Basic Med Sci. 2018;21:1305\u201315.","journal-title":"Iran J Basic Med Sci"},{"key":"7132_CR37","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.lfs.2017.09.044","volume":"191","author":"F Rostamzadeh","year":"2017","unstructured":"Rostamzadeh F, Najafipour H, Yeganeh-Hajahmadi M, Esmaeili-mahani S, Joukar S, Iranpour M. Heterodimerization of apelin and opioid receptors and cardiac inotropic and lusitropic effects of apelin in 2K1C hypertension: role of pERK1\/2 and PKC. Life Sci. 2017;191:24\u201333.","journal-title":"Life Sci"},{"key":"7132_CR38","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/1440-1681.12860","volume":"45","author":"F Rostamzadeh","year":"2018","unstructured":"Rostamzadeh F, Najafipour H, Yeganeh-Hajahmadi M, Joukar S. Opioid receptors mediate inotropic and depressor effects of apelin in rats with 2K1C-induced chronic renovascular hypertension. Clin Exp Pharmacol Physiol. 2018;45:187\u201397.","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"7132_CR39","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1161\/01.CIR.75.2.443","volume":"75","author":"CS Liang","year":"1987","unstructured":"Liang CS, Imai N, Stone CK, Woolf PD, Kawashima S, Tuttle RR. The role of endogenous opioids in congestive heart failure: effects of nalmefene on systemic and regional hemodynamics in dogs. Circulation. 1987;75:443\u201351.","journal-title":"Circulation."},{"key":"7132_CR40","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/BF02258370","volume":"8","author":"TM Wong","year":"2001","unstructured":"Wong TM, Shan J. Modulation of sympathetic actions on the heart by opioid receptor stimulation. J Biomed Sci. 2001;8:299\u2013306.","journal-title":"J Biomed Sci"},{"key":"7132_CR41","doi-asserted-by":"crossref","first-page":"205S","DOI":"10.1016\/S0895-7061(99)00103-X","volume":"12","author":"MR Weir","year":"1999","unstructured":"Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999;12:205S\u201313S.","journal-title":"Am J Hypertens"},{"key":"7132_CR42","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1007\/s00134-012-2531-2","volume":"38","author":"CA Schmittinger","year":"2012","unstructured":"Schmittinger CA, Torgersen C, Luckner G, Schr\u00f6der DCH, Lorenz I, D\u00fcnser MW. Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study. Intensive Care Med. 2012;38:950\u20138.","journal-title":"Intensive Care Med"},{"key":"7132_CR43","doi-asserted-by":"crossref","first-page":"H84","DOI":"10.1152\/ajpheart.2001.281.1.H84","volume":"281","author":"R Shahani","year":"2001","unstructured":"Shahani R, Klein LV, Marshall JG, Nicholson S, Rubin BB, Walker PM, et al. Hemorrhage-induced alpha-adrenergic signaling results in myocardial TNF-alpha expression and contractile dysfunction. Am J Physiol-Heart C. 2001;281:H84\u201392.","journal-title":"Am J Physiol-Heart C"},{"key":"7132_CR44","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1292\/jvms.68.227","volume":"68","author":"M Shimizu","year":"2006","unstructured":"Shimizu M, Tanaka R, Uchida M, et al. Effect of angiotensin II type 1 receptor blocker on cardiac angiotensin-converting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters. J Vet Med Sci. 2006;68:227\u201333.","journal-title":"J Vet Med Sci"},{"key":"7132_CR45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0184161","volume":"12","author":"M Shaqura","year":"2017","unstructured":"Shaqura M, Mohamed DM, Aboryag NB, Bedewi L, Dehe L, Treskatsch S, et al. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats. PLoS One. 2017;12:e0184161.","journal-title":"PLoS One"},{"key":"7132_CR46","doi-asserted-by":"crossref","first-page":"6894040","DOI":"10.1155\/2017\/6894040","volume":"2017","author":"NB Aboryag","year":"2017","unstructured":"Aboryag NB, Mohamed DM, Dehe L, et al. Histopathological changes in the kidney following congestive heart failure by volume overload in rats. Oxidative Med Cell Longev. 2017;2017:6894040\u201310.","journal-title":"Oxidative Med Cell Longev"},{"key":"7132_CR47","first-page":"423","volume":"272","author":"K Raynor","year":"1995","unstructured":"Raynor K, Kong H, Mestek A, et al. Characterization of the cloned human mu opioid receptor. J Pharmacol Exp Ther. 1995;272:423\u20138.","journal-title":"J Pharmacol Exp Ther"},{"key":"7132_CR48","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s40263-013-0096-4","volume":"27","author":"MJ Niciu","year":"2013","unstructured":"Niciu MJ, Arias AJ. Targeted opioid receptor antagonists in the treatment of alcohol use disorders. CNS Drugs. 2013;27:777\u201387.","journal-title":"CNS Drugs"},{"key":"7132_CR49","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/sj.bjp.0706247","volume":"145","author":"EA Walker","year":"2005","unstructured":"Walker EA, Sterious SN. Opioid antagonists differ according to negative intrinsic efficacy in a mouse model of acute dependence. Br J Pharmacol J. 2005;145:975\u201383.","journal-title":"Br J Pharmacol J"},{"key":"7132_CR50","first-page":"1121","volume":"278","author":"PJ Emmerson","year":"1996","unstructured":"Emmerson PJ, Clark MJ, Mansour A, Akil H, Woods JH, Medzihradsky F. Characterization of opioid agonist efficacy in a C6 glioma cell line expressing the mu opioid receptor. J Pharmacol Exp Ther. 1996;278:1121\u20137.","journal-title":"J Pharmacol Exp Ther"}],"container-title":["Cardiovascular Drugs and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10557-020-07132-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10557-020-07132-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10557-020-07132-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T03:59:34Z","timestamp":1625716774000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10557-020-07132-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,23]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["7132"],"URL":"https:\/\/doi.org\/10.1007\/s10557-020-07132-4","relation":{},"ISSN":["0920-3206","1573-7241"],"issn-type":[{"value":"0920-3206","type":"print"},{"value":"1573-7241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,23]]},"assertion":[{"value":"14 December 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This study was approved by the local animal care committee (Landesamt f\u00fcr Gesundheit und Soziales, Berlin, Germany; G0144\/12) and was performed according to the European Directive introducing new animal welfare and care guidelines (2010\/63\/EU).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}}]}}