Tolvaptan attenuates left ventricular fibrosis after acute myocardial infarction in rats

Abstract. 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. © the japanese pharmacological society.