Effect of LCZ696, a dual angiotensin receptor neprilysin inhibitor, on isoproterenol-induced cardiac hypertrophy, fibrosis, and hemodynamic change in rats.

Abstract:

BACKGROUND:Recent clinical studies have shown that treatment with LCZ696, a complex containing the angiotensin receptor blocker valsartan and neprilysin inhibitor sacubitril, improves the prognosis of heart failure patients with a reduced ejection fraction. This study evaluated whether LCZ696 affects left ventricular hypertrophy, fibrosis, and hemodynamics in isoproterenol (ISO)-treated rats compared with valsartan alone. METHODS:Male Wistar rats received subcutaneous saline (n = 10), subcutaneous ISO (2.4 mg/kg/day; n = 10), subcutaneous ISO + oral LCZ696 (60 mg/kg/day; n = 20) (ISO-LCZ), or subcutaneous ISO + oral valsartan (30 mg/kg/day; n = 20) (ISO-VAL) for 7 days. RESULTS:LCZ696 and valsartan did not significantly reduce the increased heart weight/body weight ratio in rats treated with ISO. Echocardiography showed that the deceleration time shortened by ISO was restored by LCZ696 but not valsartan alone (p = 0.01 vs. the ISO group). Histological analysis showed that cardiac interstitial fibrosis increased by ISO was decreased significantly by LCZ696 but not valsartan alone (control: 0.10 ± 0.14%; ISO: 0.41 ± 0.32%; ISO-LCZ: 0.19 ± 0.23% [p < 0.01 vs. the ISO group]; ISO-VAL: 0.34 ± 0.23% [p = 0.34 vs. the ISO group]). Quantitative polymerase chain reaction showed that mRNA expression of Tgfb1, Col1a1, Ccl2, and Anp increased by ISO was significantly attenuated by LCZ696 but not valsartan alone (p < 0.05 vs. the ISO group). CONCLUSIONS:LCZ696 improves cardiac fibrosis, but not hypertrophy, caused by continuous exposure to ISO in rats.

journal_name

Cardiol J

journal_title

Cardiology journal

authors

Miyoshi T,Nakamura K,Miura D,Yoshida M,Saito Y,Akagi S,Ohno Y,Kondo M,Ito H

doi

10.5603/CJ.a2018.0048

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

575-583

issue

5

issn

1897-5593

pii

VM/OJS/J/56457

journal_volume

26

pub_type

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