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Tolvaptan Attenuates Left Ventricular Fibrosis After Acute Myocardial Infarction in Rats.
MedLine Citation:
PMID:  24005048     Owner:  NLM     Status:  Publisher    
Tolvaptan, a non-peptide V2-receptor antagonist, is a newly developed diuretic agent. Recently, we reported that tolvaptan has diuretic as well as anti-inflammatory and anti-fibrotic actions in chronic heart failure. In this study, we investigated whether tolvaptan has a cardioprotective effect in acute heart failure after myocardial infarction (MI). After MI induction, rats were randomized into 6 groups as follows: vehicle group, group treated with 15 mg∙kg(-1)∙day(-1) furosemide, 2 groups treated with 3 or 10 mg∙kg(-1)∙day(-1) tolvaptan, and 2 groups treated with 15 mg∙kg(-1)∙day(-1) furosemide combined with 3 or 10 mg∙kg(-1)∙day(-1) tolvaptan. Each agent was administered for 2 weeks, and blood pressure levels and infarct sizes were similar in all MI groups. Lower left ventricular end-systolic volumes and greater improvement of left ventricular ejection fraction were observed in the tolvaptan-treated groups compared with the vehicle group. In contrast, furosemide alone did not improve them. Sirius red staining revealed that tolvaptan significantly repressed MI-induced interstitial fibrosis in the left ventricle. MI-induced mRNA expressions related to cardiac load, inflammation, and fibrosis were significantly attenuated in the combination group. The combination treatment also repressed MI-induced mineralocorticoid receptor expression. Tolvaptan, or combination of furosemide and tolvaptan, may improve cardiac function in acute MI.
Takanori Yamazaki; Yasuhiro Nakamura; Masayuki Shiota; Mayuko Osada-Oka; Hiroyuki Fujiki; Akihisa Hanatani; Kenei Shimada; Katsuyuki Miura; Minoru Yoshiyama; Hiroshi Iwao; Yasukatsu Izumi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-9-03
Journal Detail:
Title:  Journal of pharmacological sciences     Volume:  -     ISSN:  1347-8648     ISO Abbreviation:  J. Pharmacol. Sci.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-9-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101167001     Medline TA:  J Pharmacol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Cardiovascular Medicine, Osaka City University Medical School, Japan.
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