{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:09:57Z","timestamp":1761059397408,"version":"3.40.3"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:sec><jats:title>Background\u2014<\/jats:title><jats:p>Arginine vasopressin, which promotes the reabsorption of renal water is increased in chronic heart failure. Here, we compared the effects of tolvaptan, a newly developed nonpeptide V<jats:sub>2<\/jats:sub>receptor antagonist, with those of furosemide, a loop diuretic, and a combination of these 2 agents in rats with left ventricular dysfunction after myocardial infarction (MI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results\u2014<\/jats:title><jats:p>After 10 weeks of MI induction, the rats were separated them into the following 6 groups adjusted to the infarct size: a vehicle group, a group treated with 15 mg\u00b7kg<jats:sup>-1<\/jats:sup>\u00b7day<jats:sup>-1<\/jats:sup>of furosemide, 2 groups treated with 3 or 10 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>of tolvaptan; and 2 groups treated with 15 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>of furosemide plus 3 or 10 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>tolvaptan. Each treatment agent was administered for 4 weeks, and all groups had similar blood pressure levels and infarct size. The tolvaptan-treated groups were found to have lower levels of left ventricular end-diastolic and systolic cardiac volumes than the vehicle group did. Furthermore, the improvement in the ejection fraction in the tolvaptan-treated groups was significantly greater than those in the vehicle group. ED-1 immunostaining and Sirius red staining revealed that tolvaptan significantly repressed MI-induced macrophage infiltration and interstitial fibrosis in the left ventricle, respectively. Tolvaptan attenuated the MI-induced mRNA expressions of atrial and brain natriuretic peptides, monocyte chemotactic protein-1, transforming growth factor-\u03b21, arginine vasopressin V<jats:sub>1a<\/jats:sub>receptor, and endothelin-1 in the marginal infarct region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\u2014<\/jats:title><jats:p>Tolvaptan may improve cardiac dysfunction after MI, which is partially mediated by the suppression of V<jats:sub>1a<\/jats:sub>receptor, neurohumoral activation and inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1161\/circheartfailure.112.968750","type":"journal-article","created":{"date-parts":[[2012,9,15]],"date-time":"2012-09-15T11:31:38Z","timestamp":1347708698000},"page":"794-802","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Tolvaptan Improves Left Ventricular Dysfunction after Myocardial Infarction in Rats"],"prefix":"10.1161","volume":"5","author":[{"given":"Takanori","family":"Yamazaki","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine and Cardiology (T.Y., Y.N., A.H., K.S., M.Y.), and Department of Pharmacology (Y.I., N.Y., M.O., M.S., H.I.), Osaka City University Medical School, Osaka, Japan; and First Institute of New Drug Discovery, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan (H.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasukatsu","family":"Izumi","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Cardiology (T.Y., Y.N., A.H., K.S., M.Y.), and Department of Pharmacology (Y.I., N.Y., M.O., M.S., H.I.), Osaka City University Medical School, Osaka, Japan; and First Institute of New Drug Discovery, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan (H.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Cardiology (T.Y., Y.N., A.H., K.S., M.Y.), and Department of Pharmacology (Y.I., N.Y., M.O., M.S., H.I.), Osaka City University Medical School, Osaka, Japan; and First Institute of New Drug Discovery, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan (H.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Yamashita","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Cardiology (T.Y., Y.N., A.H., K.S., M.Y.), and Department of Pharmacology (Y.I., N.Y., M.O., M.S., H.I.), Osaka City University Medical School, Osaka, Japan; and First Institute of New Drug Discovery, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan (H.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Fujiki","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Cardiology (T.Y., Y.N., A.H., K.S., M.Y.), and Department of Pharmacology (Y.I., N.Y., M.O., M.S., H.I.), Osaka City University Medical School, Osaka, Japan; and First Institute of New Drug Discovery, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan (H.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayuko","family":"Osada-Oka","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Cardiology (T.Y., Y.N., A.H., K.S., M.Y.), and Department of Pharmacology (Y.I., N.Y., M.O., M.S., H.I.), Osaka City University Medical School, Osaka, Japan; and First Institute of New Drug Discovery, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan (H.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Shiota","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine and Cardiology (T.Y., Y.N., A.H., K.S., M.Y.), and Department of Pharmacology (Y.I., N.Y., M.O., M.S., H.I.), Osaka City University Medical School, Osaka, Japan; and First Institute of New Drug Discovery, Otsuka Pharmaceutical Co. 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