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Effects of Low-Dose Sacubitril/Valsartan on Different Stages of Cardiac Hypertrophy in Salt-Loaded Hypertensive Rats

Hamano, Go, MD*; Yamamoto, Koichi, MD, PhD*; Takami, Yoichi, MD, PhD*; Takeshita, Hikari, PhD*; Shimosato, Takashi, PhD; Moritani, Toshinori, BS; Rakugi, Hiromi, MD, PhD*

Journal of Cardiovascular Pharmacology: May 2019 - Volume 73 - Issue 5 - p 282–289
doi: 10.1097/FJC.0000000000000662
Original Article

Background: Sacubitril/valsartan was shown to attenuate the development of cardiac hypertrophy with enhanced blood pressure reduction compared with valsartan alone in animal models. We investigated whether a low-dose sacubitril/valsartan has blood pressure–independent effects on cardiac hypertrophy and pulmonary edema using a rat model of hypertension and obesity.

Methods and Results: In plan 1, male SHR/NDmcr-cp rats fed normal or phase-increased high salt were treated with vehicle, 6-mg/kg sacubitril/valsartan or 3-mg/kg valsartan, for 6 months. In plan 2, after high-salt loading for 6 months, drugs were administered for 4 months. Antihypertensive effects of the 2 drugs were similar during all study periods. In plan 1 with normal salt, there were no differences between treatments in the left ventricle weight/body weight (BW), or lung weight/BW as an index of cardiac hypertrophy or pulmonary edema, respectively. These indexes were smaller in high-salt-fed rats with sacubitril/valsartan than vehicle. In plan 2, both indexes did not differ between vehicle and sacubitril/valsartan. Ventricle weight/BW was lower in valsartan than sacubitril/valsartan. In plan 2, gene markers of cardiac dysfunction were upregulated by sacubitril/valsartan compared with the other groups.

Conclusions: Low-dose sacubitril/valsartan may have different effects depending on the stage of cardiac hypertrophy in rats.

*Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; and

Research Department, NISSEI BILIS Co, Ltd, Shiga, Japan.

Reprints: Koichi Yamamoto, MD, PhD, Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan (e-mail:

This study was financially supported by Novartis Pharma K.K., Japan. Sacubitril/valsartan and valsartan were provided by Novartis AG.

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Received December 18, 2018

Accepted January 23, 2019

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