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

Cell Physiol Biochem. 2024 Feb 27;58(1):83-103. doi: 10.33594/000000684.

Abstract

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 real-time PCR, total proteome analysis, and multiplex immunoassay.

Results: Data analysis revealed the up-regulation of Il 6 gene in the microcirculation of high-salt-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 ω-6) and α-linolenic (C18:3 ω-3) acid, and increased levels of palmitoleic acid (C16:1 ω-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.

Keywords: Inflammation ; Oxidative stress ; Regulatory T cells ; Sodium chloride ; T helper 17 cells ; Rats.

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Diet
  • Fatty Acids
  • Inflammation
  • Male
  • Proteome
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride* / pharmacology
  • Sodium Chloride, Dietary*
  • T-Lymphocytes, Regulatory

Substances

  • Sodium Chloride, Dietary
  • Sodium Chloride
  • Fatty Acids
  • Proteome
  • Angiotensin II