Sodium as an Important Regulator of Immunometabolism

Abstract

Salt sensitivity concerns blood pressure alterations after a change in salt intake (sodium chloride). The heart is a pump, and vessels are tubes; sodium can affect both. A high salt intake increases cardiac output, promotes vascular dysfunction and capillary rarefaction, and chronically leads to increased systemic vascular resistance. More recent findings suggest that sodium also acts as an important second messenger regulating energy metabolism and cellular functions. Besides endothelial cells and fibroblasts, sodium also affects innate and adaptive immunometabolism, immune cell function, and influences certain microbes and microbiota-derived metabolites. We propose the idea that the definition of salt sensitivity should be expanded beyond high blood pressure to cellular and molecular salt sensitivity.

Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy

“…In the last 20 years, attention has increasingly been paid to the role of innate immune cells and their proinflammatory responses in salt-sensitive hypertension. 51,52 As previously reviewed, 53,54 innate and adaptive immunometabolism has been found to be impacted by sodium intake. Immunometabolism involves understanding of how the metabolic processes within immune cells influence their function and how immune responses, in turn, impact cellular metabolism.…”

Tangram of Sodium and Fluid Balance

“…If present, they would likely to be smaller than initially suggested, but lack of magnitude does not equal lack of biological relevance: excess Na + can modulate multiple immune cells and polarize them toward an inflammatory phenotype, as extensively reviewed elsewhere. 94 , 95 Furthermore, even mild increases reflecting repeated (dietary) insults 96 or long-term mishandling may eventually be pathogenic over a life span. Recently, serum Na + values as low as the upper limits of normal were associated with long-term risk of developing left ventricular hypertrophy and heart failure in a population-based prospective cohort study, 97 consistent with old cellular studies.…”

Dietary Salt Restriction and Adherence to the Mediterranean Diet: A Single Way to Reduce Cardiovascular Risk?

“…Accordingly, the administration of an AT1-R blocker during salt loading inhibits some detrimental effects mediated by this receptor (e.g., by improving the cardiovascular function and reducing aortic collagen accumulation) [66,68]. Also, chronic inflammation during excess salt intake may contribute to cardiovascular damage [9,69]. Indeed, mechanical stimuli due to high BP lead to a vascular inflammatory response, which involves both innate and adaptive immunity [9,70].…”

“…Also, chronic inflammation during excess salt intake may contribute to cardiovascular damage [9,69]. Indeed, mechanical stimuli due to high BP lead to a vascular inflammatory response, which involves both innate and adaptive immunity [9,70].…”

“…Excess salt intake has detrimental effects on endothelial function, contributes to the salt sensitivity of BP, activates the sympathetic nervous system, and is involved in the inflammatory response, modulating innate and adaptive immunity [9,10]. There is experimental evidence of structural and functional alterations induced by high-salt regimens in the arterial wall above and beyond the effect of high BP [10].…”