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Original Article

Korean J Physiol Pharmacol 2021; 25(1): 27-38

Published online January 1, 2021 https://doi.org/10.4196/kjpp.2021.25.1.27

Copyright © Korean J Physiol Pharmacol.

Gamma-aminobutyric acid-salt attenuated high cholesterol/high salt diet induced hypertension in mice

Myeongjoo Son1,2,#, Seyeon Oh2,#, Hye Sun Lee2, Junwon Choi1,2, Bae-Jin Lee3, Joung-Hyun Park3, Chul Hyun Park4, Kuk Hui Son4,*, and Kyunghee Byun1,2,*

1Department of Anatomy and Cell Biology, Gachon University College of Medicine, 2Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, 3Marine Bioprocess Co., Ltd., Busan 46048, 4Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea

Correspondence to:Kyunghee Byun
E-mail: khbyun1@gachon.ac.kr
Kuk Hui Son
E-mail: dr632@gilhospital.com
#These authors contributed equally to this work.

Received: March 9, 2020; Revised: October 4, 2020; Accepted: October 11, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Excessive salt intake induces hypertension, but several gamma-aminobutyric acid (GABA) supplements have been shown to reduce blood pressure. GABAsalt, a fermented salt by L. brevis BJ20 containing GABA was prepared through the post-fermentation with refined salt and the fermented GABA extract. We evaluated the effect of GABA-salt on hypertension in a high salt, high cholesterol diet induced mouse model. We analyzed type 1 macrophage (M1) polarization, the expression of M1 related cytokines, GABA receptor expression, endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) proliferation, and medial thicknesses in mice model. GABA-salt attenuated diet-induced blood pressure increases, M1 polarization, and TNF-α and inducible nitric oxide synthase (NOS) levels in mouse aortas, and in salt treated macrophages in vitro. Furthermore, GABA-salt induced higher GABAB receptor and endothelial NOS (eNOS) and eNOS phosphorylation levels than those observed in salt treated ECs. In addition, GABA-salt attenuated EC dysfunction by decreasing the levels of adhesion molecules (E-selectin, Intercellular Adhesion Molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) and of von Willebrand Factor and reduced EC death. GABA-salt also reduced diet-induced reductions in the levels of eNOS, phosphorylated eNOS, VSMC proliferation and medial thickening in mouse aortic tissues, and attenuated Endothelin-1 levels in salt treated VSMCs. In summary, GABA-salt reduced high salt, high cholesterol diet induced hypertension in our mouse model by reducing M1 polarization, EC dysfunction, and VSMC proliferation.

Keywords: Blood pressure, Endothelial cells, Gamma-aminobutyric acid (GABA)-salt, Macrophage polarization, Smooth muscle cells