The Effects of Elevated Sodium on Mitochondrial Function in Peripheral Blood Mononuclear Cells

Abstract

INTRODUCTIONDiets high in sodium are associated with impaired vascular function independent of blood pressure. Recent data suggests that sodium accumulation from high salt diets reduces mitochondrial respiration in monocytes and macrophages, resembling what occurs during an inflammatory response. A similar response in circulating peripheral blood mononuclear cells (PBMCs) could implicate systemic inflammation as a mechanism contributing to high salt‐induced vascular dysfunction. Therefore, we aimed to test the hypothesis that exposure to a high sodium environment reduces PBMC mitochondrial respiration.METHODSPBMCs were separated from whole blood of ten healthy subjects (7 men/3 women, 18‐30 years, blood pressure ≤ 130/80mmHg; BMI < 30 kg/m2). PBMCs were then seeded at 2x105 cells/well in Poly‐D‐lysine treated cell culture plates. Plated cells were incubated for 24 hours in RPMI 1640 medium with 10% FBS at 137.7 mM sodium (normal sodium, NS) and 180 mM sodium (high sodium, HS). Basal, maximal, and ATP‐linked oxygen consumption rates were assessed post‐incubation by respirometry assay via Seahorse XFp analyzer (Agilent). Spare respiratory capacity was calculated as the difference between maximal and basal oxygen consumption rate.RESULTSBasal oxygen consumption rate was significantly reduced in HS compared to NS (65.0 ± 12.7 vs. 39.6 ± 6.5 pmol/min, p = 0.03), as was maximal oxygen consumption rate (198.3 ± 32.6 vs. 148.4 ± 27.2 pmol/min, p = 0.008). Basal ATP‐linked oxygen consumption rate was also significantly reduced in HS compared to NS (57.3 ± 9.8 vs. 34.4 ± 5.4 pmol/min, p = 0.01). Spare respiratory capacity in HS was significantly reduced compared to NS (133.2 ± 23.4 vs. 108.8 ± 21.2 pmol/min, p = 0.03).CONCLUSIONReduced basal and maximal oxygen consumption rates and spare respiratory capacity provide evidence that elevated sodium exposure reduces PBMC mitochondrial respiration. Additionally, high sodium exposure reduced ATP‐linked respiration potentially indicating alterations in PBMC energetics, resembling what occurs during inflammation. Collectively, our preliminary findings warrant further investigation into the role of sodium induced mitochondrial dysfunction in PBMCs as a potential mechanism contributing to high salt‐induced vascular dysfunction.