Abstract Body: Background:
Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular mortality. However, the mechanisms by which salt exposure affects blood pressure in SSBP are still unclear. We have shown that under high sodium (Na⁺) concentrations, Na⁺ enters antigen-presenting cells (APCs) via epithelial Na⁺ channel (ENaC), which leads to isolevuglandin (IsoLG) production and hypertension. Baseline %IsoLG+ APC correlates with SSBP. While the exact location where APCs are activated by salt and trigger an inflammatory response remains to be elucidated, muscle and skin are proposed as potential sites. We hypothesize that muscle and skin Na⁺ levels are associated with SSBP.
Methods: We assessed SSBP in 30 hypertensive subjects using an inpatient salt loading and depletion protocol. Flow cytometry was used to identify IsoLG-containing APCs; dendritic cells (DCs), classic (CD14+16-), non-classic (CD14-16+), and intermediate (CD14+16+) monocytes. Salt loading was achieved through saline infusion and a high-salt diet (460mmol/24 hours), while salt depletion was achieved via diuretic administration (furosemide 40mg x3) and a low-salt diet (10mmol/24hours). Baseline muscle and skin Na⁺ levels were assessed with the ²³Na MRI technique. Spearman's correlation was used to analyze the associations. Demographic data are presented with mean and standard error of the mean.
Results: Participants’ age was 53 ± 1.34 years, 53% female, baseline blood pressure was 140.2 ± 2.62 / 87.30 ± 1.77 mmHg, and salt sensitivity index was 3.72 ± 1.4 mmHg. We found an inverse correlation between baseline muscle Na⁺ levels and the decrease in IsoLGs from salt loading to depletion (ΔIsoLGs) in DCs (r=-0.50, p=0.007), intermediate (r=-0.42 p=0.0284) and non-classic monocytes (r=-0.39 p=0.0432), but not in classical monocytes. Skin Na⁺ levels were not correlated with any of these measures. There was a decreasing trend of salt sensitivity index with increasing muscle Na⁺, although this correlation did not reach statistical significance (r=-0.35 p=0.0686)
Conclusion: This highlights the potential importance of muscle Na⁺ in SSBP, such that patients with lower muscle Na⁺ exhibited a higher trend of salt sensitivity index and increased variability in IsoLG+ APCs. Moreover, baseline tissue Na⁺ assessment may emerge as a potential tool for evaluating the degree of salt sensitivity and IsoLG activation in SSBP.