Chronic high‑salt intake induces cardiomyocyte autophagic vacuolization during left ventricular maladaptive remodeling in spontaneously hypertensive rats

Ying Bi; Guo-Hong Yang; Zhao-Zeng Guo; Wei Cai; Shao-Bo Chen; Xin Zhou; Yu-Ming Li

doi:10.3892/etm.2023.11847

Chronic high‑salt intake induces cardiomyocyte autophagic vacuolization during left ventricular maladaptive remodeling in spontaneously hypertensive rats

Exp Ther Med. 2023 Feb 16;25(4):148. doi: 10.3892/etm.2023.11847. eCollection 2023 Apr.

Authors

Ying Bi^{1

2}, Guo-Hong Yang², Zhao-Zeng Guo², Wei Cai², Shao-Bo Chen², Xin Zhou^{2

3}, Yu-Ming Li^{2

4}

Affiliations

¹ Department of Internal Medicine, Tianjin Corps Hospital of The Chinese People's Armed Police Forces, Tianjin 300163, P.R. China.
² Institute of Prevention and Treatment of Cardiovascular Diseases in Alpine Environment of Plateau, Characteristic Medical Center of The Chinese People's Armed Police Forces, Tianjin 300162, P.R. China.
³ Department of Cardiovascular Diseases, General Hospital Tianjin Medical University, Tianjin 300052, P.R. China.
⁴ Department of Cardiovascular Diseases, TEDA International Cardiovascular Hospital, Tianjin 300457, P.R. China.

Abstract

The role of autophagy in high-salt (HS) intake associated hypertensive left ventricular (LV) remodeling remains unclear. The present study investigated the LV autophagic change and its association with the hypertensive LV remodeling induced by chronic HS intake in spontaneously hypertensive rats (SHR). Wistar Kyoto (WKY) rats and SHR were fed low-salt (LS; 0.5% NaCl) and HS (8.0% NaCl) diets and were subjected to invasive LV hemodynamic analysis after 8, 12 and 16 weeks of dietary intervention. Reverse transcription-quantitative PCR and western blot analysis were performed to investigate the expression of autophagy-associated key components. The LV morphologic staining was performed at the end of the study. The rat H9c2 ventricular myoblast cell-associated experiments were performed to explore the mechanism of HS induced autophagic change. A global autophagy-associated key component, as well as increased cardiomyocyte autophagic vacuolization, was observed after 12 weeks of HS intake. During this period, the heart from HS-diet-fed SHR exhibited a transition from compensated LV hypertrophy to decompensation, as shown by progressive impairment of LV function and interstitial fibrosis. Myocardial extracellular [Na⁺] and the expression of tonicity-responsive enhancer binding protein (TonEBP) was significantly increased in HS-fed rats, indicating myocardial interstitial hypertonicity by chronic HS intake. The global autophagic change and overt deterioration of LV function were not observed in LS-fed SHR and HS-fed WKY rats. The study of rat H9c2 cardiomyocytes demonstrated a cytosolic [Na⁺] elevation-mediated, reactive oxygen species-dependent the autophagic change occurred when exposed to an increased extracellular [Na⁺]. The present findings demonstrated that a myocardial autophagic change participates in the maladaptive LV remodeling induced by chronic HS intake in SHR, which provides a possible target for future intervention studies on HS-induced hypertensive LV remodeling.

Keywords: autophagy; heart failure; hypertension; oxidative stress; spontaneously hypertensive rat.

Grants and funding

Funding: The present study was supported by the National Natural Science Foundation of China (grant no. 81600328), the National Key R&D Program of China (grant nos. 2017YFC1307600 and 2017YFC1307602) and the Tianjin Municipal Science and Technology Committee (grant nos. 16JCQNJC11800, 15ZXJZSY00010 and 16ZXMJSY00130).