Sodium restriction modulates innate immunity and prevents cardiac remodeling in a rat model of metabolic syndrome

Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1568-1574. doi: 10.1016/j.bbadis.2017.02.026. Epub 2017 Feb 27.


In the view of the relationships between excessive sodium intake, immunity and target organ damage, we hypothesized that reduction in dietary sodium would be beneficial in the prevention of cardiac alterations through a restrained local immunity response in a rat model of metabolic syndrome. Sprague-Dawley rats were fed a 60% fructose diet with either a normal sodium (0.64% NaCl) or a low sodium content (<0.01% NaCl) for 8weeks. After 4weeks, rats were infused or not with angiotensin II (200ng·kg-1·min-1, sc) for 4weeks. Tail-cuff blood pressure was determined in conscious rats. Heart and left ventricle weight, cardiomyocyte size, and cardiac fibrosis were evaluated. We performed a transcriptomic analysis in order to identify differentially regulated cardiac mRNAs between normal and low sodium diets. We validated those results using qPCR and immunohistochemistry. Angiotensin II-induced blood pressure rise was blunted (~50%) in the low-sodium fed rats while cardiac hypertrophy and fibrosis were prevented. Transcriptomic analysis revealed 66 differentially regulated genes including 13 downregulated genes under the low sodium diet and implicated in the innate immune response. This was confirmed by reduced cardiac macrophages infiltration under the low sodium diet. Dietary sodium restriction prevents structural alterations of the heart of rats with fructose-induced insulin resistance and angiotensin II-hypertension. The reduction of cardiac inflammation and macrophage infiltration suggests that innate immunity has an important role in the beneficial effect of sodium restriction on cardiac remodeling.

Keywords: Cardiac hypertrophy; Fibrosis; Inflammation; Innate immunity; Low sodium diet; Macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly* / diet therapy
  • Cardiomegaly* / immunology
  • Diet, Sodium-Restricted*
  • Dietary Carbohydrates / adverse effects*
  • Dietary Carbohydrates / pharmacology
  • Disease Models, Animal
  • Fibrosis
  • Fructose / adverse effects*
  • Fructose / pharmacology
  • Immunity, Innate*
  • Metabolic Syndrome* / chemically induced
  • Metabolic Syndrome* / diet therapy
  • Metabolic Syndrome* / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride, Dietary / adverse effects
  • Sodium Chloride, Dietary / pharmacology


  • Dietary Carbohydrates
  • Sodium Chloride, Dietary
  • Fructose