title: 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.
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Medical School, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiota
authors.forename: Mayuko
authors.initials: M
authors.lastname: Osada-Oka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiki
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hanatani
authors.forename: Kenei
authors.initials: K
authors.lastname: Shimada
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005355:Fibrosis; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology*; D006352:Heart Ventricles / Q000473:pathology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017208:Rats, Wistar; D000077602:Tolvaptan; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D001552:Benzazepines; D000077602:Tolvaptan; D005665:Furosemide