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Tolvaptan Improves Left Ventricular Dysfunction after Myocardial Infarction in Rats.
MedLine Citation:
PMID:  22984091     Owner:  NLM     Status:  Publisher    
BACKGROUND: -Arginine vasopressin (AVP), which promotes the reabsorption of renal water is increased in chronic heart failure. Here, we compared the effects of tolvaptan, a newly developed non-peptide V(2) receptor antagonist, with those of furosemide, a loop diuretic, and a combination of these 2 agents in rats with left ventricular (LV) dysfunction after myocardial infarction (MI). METHODS AND RESULTS: -After 10 week of MI induction, rats were separated them into the following 6 groups adjusted to the infarct size: a vehicle group, a group treated with 15 mg·kg(-1)·day(-1) of furosemide; 2 groups treated with 3 or 10 mg·kg(-1)·day(-1) of tolvaptan, and 2 groups treated with 15 mg·kg(-1)·day(-1) of furosemide plus 3 or 10 mg(-)·kg(-1)·day(-1) 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 LV end-diastolic and systolic cardiac volumes than the vehicle group. 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-β1, AVP V(1a) receptor, and endothelin-1 in the marginal infarct region. CONCLUSIONS: -Tolvaptan may improve cardiac dysfunction after MI, which is partially mediated by the suppression of V(1a) receptor, neurohumoral activation and inflammation.
Takanori Yamazaki; Yasukatsu Izumi; Yasuhiro Nakamura; Naoto Yamashita; Hiroyuki Fujiki; Mayuko Osada-Oka; Masayuki Shiota; Akihisa Hanatani; Kenei Shimada; Hiroshi Iwao; Minoru Yoshiyama
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-14
Journal Detail:
Title:  Circulation. Heart failure     Volume:  -     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 Osaka City University Medical School, Osaka, Japan;
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