Abstract 15513: Tolvaptan Alone Significantly Worsend Left Ventricular Remodeling and Survival Rate via Increase of the Aquaporin 1 in Kidney in Murine Heart Failure After Myocardial Infarction

• Published in: Circulation (New York, N.Y.) Vol. 132; no. Suppl_3 Suppl 3; p. A15513
• Main Authors: Eguchi, Akiyo, Hirotani, Shinichi, Iwasaku, Toshihiro, Okuhara, Yoshitaka, Morisawa, Daisuke, Sawada, Hisashi, Oboshi, Makiko, Naito, Yoshiro, Mano, Toshihiro, Masuyama, Tohru
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 10.11.2015
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.132.suppl_3.15513

BackgroundLittle is known about the chronic effects of Tolvaptan, V2 receptor antagonist. Therefore, we examined the chronic effects of administration of tolvaptan and/or furosemide on survival, cardiac and renal histology in murine heart failure after myocardial infarction.MethodsFourteen days after ligating the left anterior descending coronary artery (MI), mice were randomly assigned to either placebo (P), Tolvaptan (T), or furosemide and T (FT) treatment. Survival rate was examined in each group. After four weeks after diuretic treatments, mice were sacrificed and cardiac histological analyses and cardiac and renal mRNA expression were examined.ResultsFirst, we compared survival rates of P- or T-treated mice. Surprisingly, the survival rate of P group was significantly higher than that of T group (73.7% vs. 58.3%, p<0.05). Four weeks after diuretic treatments, heart weight (HW)/body weight (BW) and lung W (LW)/BW were significantly higher in T group than in P group (HW/BW; 5.9 ± 0.2 vs. 6.8 ± 0.2 p <0.05, LW/BW 5.3 ± 0.2 vs. 7.8 ± 0.8 p <0.05). Next, to reduce congestion in T group, we fed the MI mice with FT containing chow. FT treatment improved survival rate compared with T treatment (61.5% vs. 71.4%, p<0.05). After four weeks of the treatment, HW/BW and LW/BW decreased in FT group compared with in T (HW/BW; 6.7 ± 0.2 vs. 5.5 ± 0.1 p <0.05, LW/BW; 7.0 ± 0.6 vs. 5.6 ± 0.2 p <0.05). FT treatment significantly suppressed myocardial fibrosis in remote myocardium compared with T treatment. Furthermore mRNA levels of ANP, BNP, and collagen I in the remote myocardium in FT group were lower compared with T group (ANP1 ± 0.1 vs. 0.5 ± 0.1 p <0.05, BNP; 1 ± 0.03 vs. 0.6 ± 0.04 p < 0.05, Collagen I; 1 ± 0.08 vs. 0.6 ± 0.1 p < 0.05). Interestingly, mRNA level of Aquaporin 1 (AQP1), which is a key transporter of free water absorption in proximal tubule, increased in T group compared with P group, and it reduced in FT group compared with T group (AQP1; 3.3 ± 0.4 vs. 4.2 ± 0.1 p < 0.05, 4.1 ± 0.05 vs. 2.0 ± 0.2 p < 0.05).ConclusionT treatment increased congestion and worsenend survival in murine heart failure. FT treatment successfully improved congestion and survival compared with T treatment. The mechanism by which T treatment failed to reduce congestion and mortality may be due to upregulation of AQP1.