Low sodium intake ameliorates hypertension and left ventricular hypertrophy in mice with primary aldosteronism

Zitian Wang; Xue Zhao; Lifang Bu; Kun Liu; Ziping Li; Huaxing Zhang; Xiaoguang Zhang; Fang Yuan; Sheng Wang; Zan Guo; Luo Shi

doi:10.3389/fphys.2023.1136574

Low sodium intake ameliorates hypertension and left ventricular hypertrophy in mice with primary aldosteronism

Front Physiol. 2023 Feb 15:14:1136574. doi: 10.3389/fphys.2023.1136574. eCollection 2023.

Authors

Zitian Wang¹, Xue Zhao¹, Lifang Bu¹, Kun Liu², Ziping Li¹, Huaxing Zhang³, Xiaoguang Zhang³, Fang Yuan^{1

4}, Sheng Wang^{1

4}, Zan Guo³, Luo Shi^{1

4}

Affiliations

¹ Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei, China.
² Department of Laboratory Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.
³ Core Facilities and Centers, Institute of Medicine and Health, Hebei Medical University, Shijiazhuang, Hebei, China.
⁴ Hebei Key Laboratory of Neurophysiology, Shijiazhuang, Hebei, China.

Abstract

The goal of this paper is to elucidate the effects of sodium restriction on hypertension and left ventricular (LV) hypertrophy in a mouse model with primary aldosteronism (PA). Mice with genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels (TASK^-/-) were used as the animal model of PA. Parameters of the LV were assessed using echocardiography and histomorphology analysis. Untargeted metabolomics analysis was conducted to reveal the mechanisms underlying the hypertrophic changes in the TASK^-/- mice. The TASK^-/- adult male mice exhibited the hallmarks of PA, including hypertension, hyperaldosteronism, hypernatremia, hypokalemia, and mild acid-base balance disorders. Two weeks of low sodium intake significantly reduced the 24-h average systolic and diastolic BP in TASK^-/- but not TASK^+/+ mice. In addition, TASK^-/- mice showed increasing LV hypertrophy with age, and 2 weeks of the low-sodium diet significantly reversed the increased BP and LV wall thickness in adult TASK^-/- mice. Furthermore, a low-sodium diet beginning at 4 weeks of age protected TASK^-/- mice from LV hypertrophy at 8-12 weeks of age. Untargeted metabolomics demonstrated that the disturbances in heart metabolism in the TASK^-/- mice (e.g., Glutathione metabolism; biosynthesis of unsaturated fatty acids; amino sugar and nucleotide sugar metabolism; pantothenate and CoA biosynthesis; D-glutamine and D-glutamate metabolism), some of which were reversed after sodium restriction, might be involved in the development of LV hypertrophy. In conclusion, adult male TASK^-/- mice exhibit spontaneous hypertension and LV hypertrophy, which are ameliorated by a low-sodium intake.

Keywords: hypertension; left ventricular hypertrophy; low sodium; myocardial metabolic; primary aldosteronism.

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (82100458), the Natural Science Foundation of Hebei province of China (C2020206050, H2021206017), the Hebei Province High-level Talent Funding Project (B2021003044), the Research Project of Science and Technology for Higher Education Institutions in Hebei Province (QN2021096), and the Innovative Projects for College Students in Hebei Province of China (USIP2020002).