Tolvaptan Attenuates Left Ventricular Fibrosis Afer Acute Myocardial Infarction in Rats  [in Japanese]

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Author(s)

Abstract

Tolvaptan, a non-peptide V<sub>2</sub>-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<sup>−1</sup>∙day<sup>−1</sup> furosemide, 2 groups treated with 3 or 10 mg∙kg<sup>−1</sup>∙day<sup>−1</sup> tolvaptan, and 2 groups treated with 15 mg∙kg<sup>−1</sup>∙day<sup>−1</sup> furosemide combined with 3 or 10 mg∙kg<sup>−1</sup>∙day<sup>−1</sup> 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.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 123(1), 58-66, 2013-09-20

    The Japanese Pharmacological Society

References:  30

Codes

  • NII Article ID (NAID)
    10031202963
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    JPN
  • Article Type
    ART
  • ISSN
    13478613
  • NDL Article ID
    024863717
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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