{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:43:36Z","timestamp":1791074616340,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Cardiac injury induced by isoprenaline produces stress. This stress can be mediated by the activated endothelin and leptin pathway; thus, the endothelin receptor antagonist CPU0213 may reverse these changes. CPU0213 is metabolized mainly by cytochrome P450 (CYP)3A, thus, erythromycin, an inhibitor of CYP3A, could affect its effects by raising its plasma levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Forty rats were divided into five groups. Group 1 rats were normal. Group 2 rats were administered isoprenaline (1 mg\/kg, s.c.) for 10 days. Groups 3, 4 and 5 were administered isoprenaline, but group 3 was given erythromycin (100 mg\/kg, p.o.) alone on days six to ten, group 4 was given CPU0213 20 mg\/kg (s.c.) on days six to ten, whilst group 5 received erythromycin plus CPU0213 on days six to ten. Measurements were conducted to observe changes in the haemodynamics, cardiac weight index, serum lactate dehydrogenase and creatine kinase levels, and expression of endothelin receptor A (ETa), leptin and its OBRb receptor.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>In isoprenaline-treated rats, cardiac hypertrophy and dysfunction were found. This was associated with upregulated myocardial leptin protein and OBRb receptor mRNA. Immunohistochemical assay of ETa was upregulated, accompanied with downregulation of FKBP12.6 (calstabin 2) in isoprenaline-treated rats. These effects were significantly reversed by CPU0213. HPLC assay presented an increased plasma level of CPU0213 by erythromycin, but no change in its effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CPU0213 improved isoprenaline-induced cardiomyopathy by modulating ETa, leptin and FKBP12.6. However, erythromycin increased plasma levels but did not change its effects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1211\/jpp.61.05.0004","type":"journal-article","created":{"date-parts":[[2010,10,14]],"date-time":"2010-10-14T13:40:05Z","timestamp":1287063605000},"page":"569-576","source":"Crossref","is-referenced-by-count":13,"title":["Stress-induced cardiac insufficiency relating to abnormal leptin and FKBP12.6 is ameliorated by CPU0213, an endothelin receptor antagonist, which is not affected by the CYP3A suppressing effect of erythromycin"],"prefix":"10.1093","volume":"61","author":[{"given":"Yu-Si","family":"Cheng","sequence":"first","affiliation":[{"name":"Research Division of Pharmacology, China Pharmaceutical University , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Zai","family":"Dai","sequence":"additional","affiliation":[{"name":"Research Division of Pharmacology, China Pharmaceutical University , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Dai","sequence":"additional","affiliation":[{"name":"Research Division of Pharmacology, China Pharmaceutical University , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,5,1]]},"reference":[{"key":"2024103109371991900_cit1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.etp.2008.03.010","article-title":"Cardioprotective activity of Ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: a biochemical and histoarchitectural evaluation","volume":"60","author":"Panda","year":"2008","journal-title":"Exp Toxicol Pathol"},{"key":"2024103109371991900_cit2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ejphar.2008.06.080","article-title":"Endothelin receptor antagonist CPU0213 and vitamin E reverse downregulation of FKBP12.6 and SERCA2a: a role of hyperphosphorylation of PKCepsilon","volume":"591","author":"Li","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"2024103109371991900_cit3","doi-asserted-by":"crossref","first-page":"7906","DOI":"10.1073\/pnas.0602133103","article-title":"Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmias","volume":"103","author":"Lehnart","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024103109371991900_cit4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1196\/annals.1341.032","article-title":"Ryanodine receptor-targeted anti-arrhythmic therapy","volume":"1047","author":"Wehrens","year":"2005","journal-title":"Ann N Y Acad Sci"},{"key":"2024103109371991900_cit5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00210-007-0134-1","article-title":"Upregulation of leptin pathway correlates with abnormal expression of SERCA2a, phospholamban and the endothelin pathway in heart failure and reversal by CPU86017","volume":"375","author":"Na","year":"2007","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"2024103109371991900_cit6","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ijcard.2008.05.018","article-title":"Downregulated FKBP12.6 expression and upregulated endothelin signaling contribute to elevated diastolic calcium and arrhythmogenesis in rat cardiomyopathy produced by 1-thyroxin","volume":"130","author":"Zhang","year":"2008","journal-title":"Int J Cardiol"},{"key":"2024103109371991900_cit7","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.atherosclerosis.2008.05.034","article-title":"Role of inflammation and oxidative stress in endothelial progenitor cell function and mobilization: therapeutic implications for cardiovascular diseases","volume":"201","author":"Tousoulis","year":"2008","journal-title":"Atherosclerosis"},{"key":"2024103109371991900_cit8","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.cardiores.2004.08.013","article-title":"Cardiac oxidative stress in acute and chronic isoproterenol-infused rats","volume":"65","author":"Zhang","year":"2005","journal-title":"Cardiovasc Res"},{"key":"2024103109371991900_cit9","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1097\/FJC.0b013e31817dfc8f","article-title":"The endothelin receptor antagonist CPU0213 is more effective than aminoguanidine to attenuate isoproterenol-induced vascular abnormality by suppressing overexpression of NADPH oxidase, ETA, ETB, and MMP9 in the vasculature","volume":"52","author":"Xu","year":"2008","journal-title":"J Cardiovasc Pharmacol"},{"key":"2024103109371991900_cit10","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1745-7254.2007.00503.x","article-title":"Improvement of chronic heart failure by dexamethasone is not associated with downregulation of leptin in rats","volume":"28","author":"Xia","year":"2007","journal-title":"Acta Pharmacol Sin"},{"key":"2024103109371991900_cit11","first-page":"552","article-title":"Endothelin receptor antagonist activity and selective blocking the ETA and ETB of compound 0213","volume":"35","author":"Dai","year":"2004","journal-title":"J China Pharm Univ"},{"key":"2024103109371991900_cit12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1745-7254.2006.00288.x","article-title":"Pharmacokinetics of CPU0213, a novel endothelin receptor antagonist, after intravenous administration in mice","volume":"27","author":"Guan","year":"2006","journal-title":"Acta Pharmacol Sin"},{"key":"2024103109371991900_cit13","first-page":"99","article-title":"Metabolic kinetics of CPU0213, an inhibitor of endothelin receptors, in rat liver microsomes","volume":"1","author":"Yang","year":"2006","journal-title":"Asian J Pharmaceut Sci"},{"key":"2024103109371991900_cit14","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1440-1681.2007.04856.x","article-title":"Effect of the endothelin receptor antagonist CPU0213, and its modulation by rifampin, on cardiac and vascular tissue following chronic isoproterenol treatment","volume":"35","author":"Luo","year":"2008","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2024103109371991900_cit15","doi-asserted-by":"crossref","first-page":"310","DOI":"10.2174\/138920008784220664","article-title":"Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4","volume":"9","author":"Zhou","year":"2008","journal-title":"Curr Drug Metab"},{"key":"2024103109371991900_cit16","first-page":"409","article-title":"Gut hyperpermiability after ischemia and reperfusion: attenuation with adrenomedullin and its binding protein treatment","volume":"1","author":"Higuchi","year":"2008","journal-title":"Int J Clin Exp Pathol"},{"key":"2024103109371991900_cit17","doi-asserted-by":"crossref","first-page":"511","DOI":"10.18388\/abp.2008_3057","article-title":"Upregulation of GRP78 and caspase-12 in diastolic failing heart","volume":"55","author":"Sun","year":"2008","journal-title":"Acta Biochim Pol"},{"key":"2024103109371991900_cit18","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1161\/01.CIR.101.20.2338","article-title":"Chronic beta-adrenergic stimulation induces myocardial proinflammatory cytokine expression","volume":"101","author":"Murray","year":"2000","journal-title":"Circulation"},{"key":"2024103109371991900_cit19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/rej.2007.0609","article-title":"Tonic beta-adrenergic drive provokes proinflammatory and proapoptotic changes in aging mouse heart","volume":"11","author":"Hu","year":"2008","journal-title":"Rejuvenation Res"},{"key":"2024103109371991900_cit20","first-page":"1061","article-title":"Could beta blockade improve outcome after injury by modulating inflammatory profiles","volume":"64","author":"Friese","year":"2008","journal-title":"J Trauma"},{"key":"2024103109371991900_cit21","doi-asserted-by":"crossref","first-page":"H2906","DOI":"10.1152\/ajpheart.01253.2006","article-title":"Endothelium-derived nitric oxide mediates the anti-adrenergic effect of human vasostatin-1 in rat ventricular myocardium","volume":"292","author":"Gallo","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2024103109371991900_cit22","doi-asserted-by":"crossref","first-page":"163","DOI":"10.2147\/vhrm.2006.2.2.163","article-title":"Leptin and hypertension in obesity","volume":"2","author":"Bravo","year":"2006","journal-title":"Vasc Health Risk Manag"},{"key":"2024103109371991900_cit23","doi-asserted-by":"crossref","first-page":"H2504","DOI":"10.1152\/ajpheart.00322.2006","article-title":"Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction","volume":"291","author":"Thakker","year":"2006","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2024103109371991900_cit24","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1161\/hc5001.101061","article-title":"Plasma leptin and the risk of cardiovascular disease in the West of Scotland Coronary Prevention Study (WOSCOPS)","volume":"104","author":"Wallace","year":"2001","journal-title":"Circulation"},{"key":"2024103109371991900_cit25","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.lfs.2005.06.039","article-title":"Leptin protects the cardiac myocyte cultures from hypoxic damage","volume":"78","author":"Erkasap","year":"2006","journal-title":"Life Sci"},{"key":"2024103109371991900_cit26","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1161\/01.CIR.0000140766.52771.6D","article-title":"Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes","volume":"110","author":"Xu","year":"2004","journal-title":"Circulation"},{"key":"2024103109371991900_cit27","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1161\/01.HYP.36.4.501","article-title":"Leptin attenuates cardiac contraction in rat ventricular myocytes. Role of NO","volume":"36","author":"Nickola","year":"2000","journal-title":"Hypertension"},{"key":"2024103109371991900_cit28","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1161\/01.HYP.0000198555.51645.f1","article-title":"Leptin regulates cardiomyocyte contractile function through endothelin-1 receptor-NADPH oxidase pathway","volume":"47","author":"Dong","year":"2006","journal-title":"Hypertension"},{"key":"2024103109371991900_cit29","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1161\/HYPERTENSIONAHA.106.083303","article-title":"Endogenous endothelin in human coronary vascular function: differential contribution of endothelin receptor types A and B","volume":"49","author":"Halcox","year":"2007","journal-title":"Hypertension"},{"key":"2024103109371991900_cit30","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/sj.bjp.0706384","article-title":"Reversal of cardiac dysfunction by selective ET-A receptor antagonism","volume":"146","author":"Allan","year":"2005","journal-title":"Br J Pharmacol"},{"issue":"Suppl","key":"2024103109371991900_cit31","doi-asserted-by":"crossref","first-page":"6761","DOI":"10.1109\/IEMBS.2006.260941","article-title":"Unraveling the mechanisms of catecholaminergic polymorphic ventricular tachycardia","author":"Iyer","year":"2006","journal-title":"Conf Proc IEEE Eng Med Biol Soc"},{"key":"2024103109371991900_cit32","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1161\/01.RES.0000192146.85173.4b","article-title":"Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death","volume":"97","author":"Jiang","year":"2005","journal-title":"Circ Res"},{"key":"2024103109371991900_cit33","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/0470029331.ch9","article-title":"Novel therapy for heart failure and exercise-induced ventricular tachycardia based on \u2018fixing\u2019 the leak in ryanodine receptors","volume":"274","author":"Marks","year":"2006","journal-title":"Novartis Found Symp"},{"key":"2024103109371991900_cit34","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1111\/j.1745-7254.2007.00650.x","article-title":"Reversal of isoproterenol-induced downregulation of phospholamban and FKBP12.6 by CPU0213-mediated antagonism of endothelin receptors","volume":"28","author":"Feng","year":"2007","journal-title":"Acta Pharmacol Sin"},{"key":"2024103109371991900_cit35","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1097\/00000542-200606000-00016","article-title":"The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning)","volume":"104","author":"Brambrink","year":"2006","journal-title":"Anesthesiology"},{"key":"2024103109371991900_cit36","first-page":"109","article-title":"Plasma concentrations in relation to clinical drug effects, Chapter 10","volume-title":"A Text Book of Clinical Pharmacology","author":"Dai","year":"2002"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1211%2Fjpp.61.05.0004","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/61\/5\/569\/60257723\/jpp.61.05.0004.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/61\/5\/569\/60257723\/jpp.61.05.0004.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T09:58:18Z","timestamp":1730368698000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/61\/5\/569\/6135972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5,1]]},"references-count":36,"aliases":["10.1211\/jpp\/61.05.0004"],"journal-issue":{"issue":"5","published-online":{"date-parts":[[2009,5,1]]},"published-print":{"date-parts":[[2009,5,1]]}},"URL":"https:\/\/doi.org\/10.1211\/jpp.61.05.0004","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2009,5]]},"published":{"date-parts":[[2009,5,1]]}}}