he Ablation of Dendritic cells prevents the upregulation of the intrarrenal Renin-Angiotensin System and renal sodium transporters in response to Angiotensin II and high salt diet

Araos PA; Hevia DE; Prado CE; Fuentes, EL; Pacheco R.; Michea LF

Abstract

Blood pressure depends on the renal sodium reabsorption mediated by the tubular transporters that are modulated by the intrarenal renin–angiotensin system (iRAS). Angiotensin II (Ang II) and a high salt diet (HS) cause hypertension (HT) and the upregulation of the iRAS and sodium transporters. Our previous studies showed that the ablation of Dendritic Cells (DC) in mice prevented the development of HT in response to AngII+HS. In the present study, we evaluated if the ablation of DCs alters the modulation of the iRAS and tubular sodium transporters by AngII+HS. CD11c.DOG mice, for selective loss of DCs (CD11cHi) cells after Diphteria Toxin (DT) injection, received vehicle, AngII+HS (AngII, 450 μg Kg/day+1% NaCl in drinking water) or AngII+HS+DT (DT, 8ng/g) during 14 days; Paired WT mice received vehicle, AngII+HS or AngII+HS+DT. We measured blood pressure (days 0, 4, 8, 14), and at day 14 we harvested tissues to measure the abundance of renal DCs (MHC-II+ and CD11c+) by inmunofluoresce, the iRAS, the sodium-proton exchanger 3 (NHE3), the sodium-chloride cotransporter (NCC) and the Epithelial Sodium Channel (αENaC) by qRT-PCR and Western blot. The injection of DT prevented the development of HT in response to AngII+HS only in CD11c.DOG mice. CD11c.DOG and WT mice showed increased abundance of DCs in the cortex (peritubular); Only the CD11c.DOG mice showed a sharp reduction of renal DCs after DT injection. Both, in WT as in CD11c.DOG mice the administration of AngII+HS increased the iRAS (in fold of induction: Angiotensinogen 1.5; Angiotensin converting enzyme 1.9; and Angiotensin II receptor type I, 5), NHE3, NCC and αENaC (in fold of induction: 4.2; 6; 2), respectively vs vehicle–treated mice (p<0.05; n=5-9). The injection of DT concomitant to AngII+HS prevented the changes in sodium transporters and iRAS in CD11c.DOG mice (p<0.05 compared to AngII+HS; n=5-9) We conclude that DCs are required for the modulation of iRAS and tubular sodium transporters by AngII+HS.

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Fecha de publicación: 2015
Año de Inicio/Término: 3-8 de Noviembre
Idioma: Ingles