Tolvaptan Attenuates Left Ventricular Fibrosis After Acute Myocardial Infarction in Rats

Journal of Pharmacological Sciences

Hiroshi Iwao²  Mayuko Osada-Oka²  Katsuyuki Miura³  Yasukatsu Izumi²  Minoru Yoshiyama¹  Yasuhiro Nakamura¹  Takanori Yamazaki¹  Akihisa Hanatani¹  Kenei Shimada¹  Masayuki Shiota²  Hiroyuki Fujiki⁴ 

[1] Department of Cardiovascular Medicine, Osaka City University Medical School, Japan;Department of Pharmacology, Osaka City University Medical School, Japan;Applied Pharmacology and Therapeutics, Osaka City University Medical School, Japan;First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Japan

关键词: arginine vasopressin;    acute myocardial infarction;    diuretic;    tolvaptan;    cardiac remodeling;   

DOI  :  10.1254/jphs.13086FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(30)Cited-By(4)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.

【 授权许可】

Unknown