Abstract 126: Antigen Presenting Cell Isolevuglandins: A Potential Diagnostic Tool For Salt Sensitivity Of Blood Pressure In Humans

Abstract

Salt sensitivity of blood pressure is an independent cardiovascular risk factor as powerful as hypertension, yet it goes untreated due to the lack of a feasible diagnostic tool. We previously found that sodium enters antigen-presenting cells (APCs) via ENaC, leading to the formation of isolevuglandins (IsoLGs). IsoLGs are highly reactive oxidative products of fatty acids and act as neoantigens to trigger inflammation in hypertension. We found that activation of APCs via IsoLG is highly variable in humans. Thus, we hypothesized that this variability in IsoLG-mediated APC activation contributes to the variability observed in human salt sensitivity of blood pressure and that IsoLGs can be used as a diagnostic tool. We measured systolic blood pressure (SBP) and IsoLG-containing APCs (dendritic cells [DC], classical, intermediate and non-classical monocytes) by flow cytometry in 14 hypertensive subjects who were off therapy for 2 weeks, before (B) and after in-patient 24 hr salt loading (HI, 460 mmol Na + ) and salt depletion (LO, 10 mmol Na + and furosemide 40 mg x 3). Salt sensitivity was assessed by ΔSBP (LO minus HI). Median age was 49, with 5 females, median BMI (IQR) of 29.8 (25.2, 39.5) kg/m 2 and screening SBP of 135.1 (130, 144.9) mmHg. The median urinary Na + excretions (IQR) were 169.6 (125, 203.3), 360.9 (324.1, 421.2) and 54.8 (36.8, 76) mmol/24h at baseline, HI and LO days, respectively. Baseline percentages of classical and non-classical monocytes with IsoLGs were positively correlated with ΔSBP (r=0.64, p=0.01 and r=0.71, p<0.01 respectively). Changes in IsoLG-containing DCs and nonclassical monocytes positively correlated with ΔSBP (r=0.60, p=0.03 and r=0.69, p=0.01 respectively). Both the baseline levels and changes in IsoLG containing APCs associated with salt sensitivity. Greater decrease in IsoLG-containing APCs predicted greater decline in blood pressure in response to salt depletion, suggesting that oxidative stress in APCs is implicated in the pathogenesis of salt sensitivity. Our results further suggest that baseline percentage of IsoLG-containing APCs may be the first predictor of salt sensitivity that does not require a protocol of salt loading and depletion. This would enable the diagnosis of salt sensitivity in clinic practice.