Abstract 132: Monocytes Activation by Salt is Associated With Cardiovascular Risk Factors

Several studies have established a relationship between hypertension and salt intake; however the mechanisms by which salt causes hypertension are poorly understood. There is also evidence that sodium (Na+) accumulates in the interstitium with aging and hypertension in concentrations exceeding the plasma. We tested the hypothesis that increased NaCl would convert human monocytes to an inflammatory phenotype and to define mechanisms involved. We exposed monocytes from 17 human volunteers to normal physiological NaCl (NS: 150 mM/L), elevated NaCl (HS: 190 mM/L), or an equiosmoloar concentration of mannitol. Exposure of human monocytes to high salt, but not mannitol, increased formation of immunogenic isolevuglandins (isoLG) (NS: 1688±384 vs Mann:1762±429 vs HS: 2381± 635 MFI p<0.002). This was associated with an increase in the dendritic cell (DC) marker CD83 (NS: 503±81 vs Mann: 530± 106 vs HS: 764 ± 136 MFI p<0.001). Exposure to high salt also stimulated production of IL-6 (NS: 2145±771, Mann: 1122±295 and HS: 5187±1146 pg/mL, p=0.04), IL-β (NS: 94±35, Mann: 62±16 and HS: 224±98 pg/mL, p=0.01) and TNF-α (NS:1.9±0.3, Mann: 3.42±1.4 and HS: 4.4±2.1, p<0.0001). In additional experiments, we found that prolonged (7 day) exposure to high salt increased surface expression of CD209, another DC marker (NS: 22±9 vs HS: 34 ± 14, p=0.001) and promoted conversion of the cells to a DC morphology. The propensity for monocytes to respond to NaCl was influence by the patient’s risk factors. The increase in IsoLG (HS-NS) correlated with pulse pressure (mmHg, r=0.51, <0.04), BMI (Kg/m2, r=0.66, p=0.005), total cholesterol (mg/dL, r=0.55, p<0.05) and glucose (mg/dL, r=0.72, p=0.003). Stepwise multivariate regression revealed that BMI and pulse pressure are independent predictors of IsoLG formation in response to salt. These findings suggest that high extracellular NaCl promotes differentiation and activation of monocytes and that these pleotropic inflammatory cells exhibit a previously undefined salt sensitivity corresponding to patients’ underlying risk factor profile.