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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
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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: kyamamoto@geriat.med.osaka-u.ac.jp).

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

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcvp.org).

Received December 18, 2018

Accepted January 23, 2019

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