Abstract

Angiotensin II (AngII) and high-salt diet (HS) cause hypertension, endothelial dysfunction and the upregulation of renal sodium transporters. Our previous studies showed that the ablation of Dendritic Cells (DCs) in mice prevented hypertension and the increased expression of renal sodium transporters. In the present study we evaluated if the ablation of DCs modified natriuresis and arterial function in AngII+HS treated mice We studied wild type (WT) mice and CD11c.DOG transgenic mice (CD11c) for the selective elimination of DCs by Diphteria Toxin (DT) injection. WT and CD11c mice were divided into 3 groups: AngII+HS (AngII=1.042 μg/Kg/min+1% NaCl in drinking water), AngII+HS+DT (DT=8ng/g) and control. Blood pressure (BP) and urinary sodium excretion was analyzed. At days 4 and 14, we made saline challenge test (injection of isotonic saline; 10% of BW) and measured 4h natriuresis. We obtained aortic rings at day 14 for vascular reactivity and endothelial function studies WT mice of AngII+HS and AngII+HS+DT groups showed similar increase of SBP. However, the injection of DT prevented the increase of SBP in CD11c mice. Telemetric studies confirmed high BP of AngII+HS CD11c mice (PAM=144±21 mmHg; SBP=160±26 mmHg, day14) that was prevented by the ablation of DCs (PAM=92.7±20 mmHg and SBP=104±26 mmHg). The AngII+HS treatment increased 24h natriuresis (19.4±7.6 µEq/g BW); the ablation of DCs further increased natriuresis (30±7.9 µEq/g BW; n=5; P<0.05) in CD11c mice. Natriuresis after saline challenge test in AngII+HS mice was similar in WT and CD11c mice at day 4. However, the DT injection in CD11c mice increased natriuresis in 27% compared to the other AngII+HS groups (P<0.05). Aortic rings showed similar vascular reactivity and endothelial function in all AngII+HS groups. The results suggest that DCs modulate tubular sodium reabsorption in response to AngII and high salt diet.