Early Low-Grade Inflammation Induced by High-Salt Diet in Sprague Dawley Rats Involves Th17/Treg Axis Dysregulation, Vascular Wall Remodeling, and a Shift in the Fatty Acid Profile

Background/Aims: Unrestricted increased table salt (NaCl) intake is associated with oxidative stress and inflammation, leading to endothelial dysfunction and atherosclerosis. However, data on salt-induced immunomodulatory effects in the earliest phase of salt loading are scarce. Methods: In the present study, an animal model of short -term salt loading was employed, including male Sprague Dawley rats consuming a high -salt diet (HSD; 4% NaCl) or standard laboratory chow (low-salt; LSD; 0.4% NaCl) during a 7 -day period. The contribution of angiotensin II (ANGII) suppression was tested by adding a group of rats on a high -salt diet receiving ANGII infusions. Samples of peripheral blood/mesenteric lymph node leukocytes, brain blood vessels, and serum samples were processed for flow cytometry, quantitative realtime PCR, total proteome analysis, and multiplex immunoassay.Results: Data analysis revealed the up -regulation of Il 6 gene in the microcirculation of highsalt -fed rats, accompanied by an increased serum level of TNF-alpha cytokine. The high -salt diet resulted in increased proportion of serum mono -unsaturated fatty acids and saturated fatty acids, reduced levels of linoleic (C18:2 omega-6) and alpha-linolenic (C18:3 omega-3) acid, and increased levels of palmitoleic acid (C16:1 omega-7). The high -salt diet had distinct, lymphoid compartment -specific effects on leukocyte subpopulations, which could be attributed to the increased expression of salt -sensitive SGK-1 kinase. Complete proteome analysis revealed high -salt -diet -induced vascular tissue remodeling and perturbations in energy metabolism. Interestingly, many of the observed effects were reversed by ANGII supplementation. Conclusion: Low-grade systemic inflammation induced by a HSD could be related to suppressed ANGII levels. The effects of HSD involved changes in Th17 and Treg cell distribution, vascular wall remodeling, and a shift in lipid and arachidonic acid metabolism. (c) 2024 The Author(s). Published by Cell Physiol Biochem Press GmbH&Co. KG