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J Cardiovasc Pharmacol. 2019 Feb 28. doi: 10.1097/FJC.0000000000000662. [Epub ahead of print]

Effects of low-dose sacubitril/valsartan on different stages of cardiac hypertrophy in salt-loaded hypertensive rats.

Author information

1
. Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine.
2
. Research Department, NISSEI BILIS Co., Ltd.

Abstract

BACKGROUND:

Sacubitril/valsartan was shown to attenuate the development of cardiac hypertrophy with enhanced blood pressure (BP) reduction compared to valsartan alone in animal models. We investigated whether a low dose sacubitril/valsartan has BP-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 phased-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 two 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 (VW/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. VW/BW was lower in valsartan than sacubitril/valsartan. In plan 2, gene markers of cardiac dysfunction were upregulated by sacubitril/valsartan compared to the other groups.

CONCLUSION:

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

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