Introduction:
Salt Sensitivity (SS) of blood pressure (BP) is an independent predictor of death due to cardiovascular disease, but its pathogenesis is poorly understood. Sodium (Na
+
) is stored in the skin and muscle interstitium. This hyperosmolar Na
+
activates monocytes
in vitro
via oxidative stress with generation of isolevuglandin (isoLG) protein adducts that are immunogenic and activate the adaptive immune system.
Methods:
Five subjects with essential hypertension discontinued all anti-hypertensive therapy for two weeks before the study. SS was assessed by an inpatient protocol of salt loading (460 mmoL/24h) and salt depletion (10 mmoL/24h, plus furosemide 40 mg x 3). Muscle and skin Na
+
contents were measured at baseline (BA) by
23
Sodium magnetic resonance imaging (
23
NaMRI). Urine and serum electrolytes, glomerular filtration rate and the % CD14
+
monocytes containing isoLG adducts using flow cytometry were obtained at BA, after salt-loading (HI) and after salt-depletion (LO). All continuous data are displayed as median (interquartile range). Spearman’s correlation was used to test associations.
Results:
Median age was 54 years (44-55), 60% of subjects were female, screening systolic BP (SBP) was 140 mmHg (134-148), diastolic BP was 88 mmHg (84-99) and BMI was 35 kg/m
2
(30-39). SBP response to salt-depletion (salt-sensitivity index, SSI) varied from -13.8 to +1.8 mmHg. %isoLG
+
CD14
+
cells were 48 (27-65) at BA, 55 (31-56) at HI, and 70 (33-72) at LO (p=0.594, by the Kruskal-Wallis test). The correlation between SSI and delta (Δ) %isoLG
LO minus HI,
was 0.86, [95% confidence interval (CI), -0.07-0.99] which may suggest conclusively as we gather more data that the greater the SSI, the larger the decrease in isoLGs by salt depletion. Muscle Na
+
content correlated with 24h urine Na
+
(BA) (r=0.90, 95% CI, 0.11-0.99), however, the correlation with BP, SSI or isoLGs was inconclusive, potentially due to the small sample size. Skin Na
+
content correlated with baseline %CD14IsoLG
+
(r=0.91; 95% CI, 0.12-0.99).
Conclusions:
Na
+
intake is a component of the determinants of muscle Na
+
. Skin Na
+
is associated with increased isoLGs in monocytes, a marker of immune cell activation. Variability in ΔCD14isoLG may serve as a biomarker for SS of BP in humans.