In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 72, No. Suppl_1 ( 2018-09)
Kurzfassung:
Salt-sensitivity is present in 50% of all hypertensive individuals. Prior studies have focused on the roles of kidney, vasculature and sympathetic activity in salt-sensitivity but the contribution of immune cells is poorly understood. We recently found that in murine dendritic cells amiloride sensitive channels sense salt and trigger NADPH oxidase-dependent formation of isolevuglandin-(IsolG)-adducts. We tested the hypothesis that human monocytes exhibit salt-sensitivity leading to activation via IsoLG-adduct formation and this is associated with cardiovascular risk factors. In a cohort of 18 subjects, we found that the sodium intake, measured by 24 hours urine excretion (UNa) was positively correlated with plasma levels of IsolGs. We also measured accumulation of interstitial sodium in 70 subjects by Magnetic Sodium Resonance and evaluated their circulating monocytes by flow cytometry. Subjects with high skin sodium had higher levels of IsoLGs in their monocytes (24±6 vs 38±6 %, p 〈 0.05) and higher expression of CD83, an activation and dendritic cell marker (0.04 ± 0.009 vs 0.12± 0.04%, p =0.04). To investigate the ability of monocytes to respond to salt, we cultured monocytes from 17 subjects in high salt environment (HS:190 mM NaCl) or normal media (NS:150mM NaCl) for 48 hours. In culture, 47% of the subjects respond to salt, denoted by an increase of at least 20% in IsoLG formation (NS: 1327±240 vs. HS: 2217±653, p =0.009) as well as increased expression of the activation markers CD83 and CD86. The subjects’ cardiovascular risk factors including pulse pressure, BMI, glucose and total cholesterol positively correlated with the amount of IsolGs produced (ΔHS-NS) in response to salt (r=0.51 p 〈 0.05, r=0.66 p=0.005, r=0.55 p 〈 0.05, p=0.72 p=0.003, respectively). Interestingly, 5 pM of Ouabain, a Na-K-ATPase blocker, increased intracellular sodium and expression of CD86 (NS: 98±11, HS: 203 ±16 vs, NS+ Ouabain: 476 ± 58 MFI, p=0.001) and CD83 (NS: 778±90, HS: 1529 ± 94 vs, NS+ Ouabain: 1649 ± 209 MFI, p=0.003). We suggest that in addition to the kidney and vasculature, human monocytes and monocyte derived cells exhibit salt sensitivity, and that this is conveyed by cardiovascular risk factors and activity of the Na-K-ATPase.
Materialart:
Online-Ressource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.72.suppl_1.088
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2018
ZDB Id:
2094210-2
