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
Background: Little 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.
Methods: Fourteen 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.
Results: First, 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 (ANP: 1 ± 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).
Conclusion: T 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.
Author Disclosures: A. Eguchi: None. S. Hirotani: None. T. Iwasaku: None. Y. Okuhara: None. D. Morisawa: None. H. Sawada: None. M. Oboshi: None. Y. Naito: None. T. Mano: None. T. Masuyama: None.
- © 2015 by American Heart Association, Inc.