Losartan Prevents The Recruitment Of Renal M1-like Macrophages And Dendritic Cells In Medulla Of Angiotensin Ii Hypertensive Mice

Immune cells play a major role in the development and progression of hypertension. Previous studies have shown that antigen presenting cells (APCs), such as macrophages (Mø) and dendritic cells (DCs) are particularly abundant in kidney. However, the relevance of these renal APCs on hypertension and whether their distribution change during the anti-hypertensive treatment remain unknow. We evaluated whether losartan (Los) treatment changes the abundance of APCs in the renal cortex and medulla in Angiotensin (Ang) II-infused mice.Male C57BL/6 mice (8-12wo) were treated with AngII (490ng/Kg/min), AngII+Los (20mg/Kg/day) or Vehicle for 14 days (n=4-6). Systolic blood pressure (SBP) was measured by the tail cuff method, and renal cortex/medulla were isolated for the measurements of: APCs (MHC-II + :CD11c + ), DCs (APCs:F4/80 - :CD64 - /CD103 + for type-1 DCs, or APCs:F4/80 - :CD64 - :CD11b + for type-2 DCs), and M1-like Mø (APCs:F4/80 - :CD64 + :CD11b + ), by flow cytometry.Los treatment prevented the increased SBP (AngII+Los=118.8±6.4 mmHg vs. AngII=158.0±21.1 mmHg; p<0.001), and the APCs recruitment in renal cortex (AngII+Los=23.2±2.7 vs. AngII=36.0±5.9%; p<0.01) and in renal medulla (Veh=16.3±7.7; AngII=26.3±4,7; AngII+Los=14.9±3.3%; p<0.05) induced by AngII. In addition, we observed an increase of DC2 and M1-like Mø recruitments in renal medulla of AngII mice (DC2 Veh =29.0±5.0 vs. DC2 AngII =45.5±7.3%; p<0.05; M1 Veh =44.8±7.5 vs. M1 AngII =58.3±5.3%; p<0.05), which were prevented by Los treatment (DC2 AngII+Los =27.1±6.8%; p<0.05; M1 AngII+Los =47.0±3.5%; p<0.05). Interestingly, we did not observe differences between groups on M1-like Mø, and DC2 populations in renal cortex. However, Los treatment prevented the increase of DC1 on renal cortex (Veh=2.1±1.4; AngII=5.2±2.4; AngII+Los=2.1±0.8%; p<0.05), without differences between groups at medullar level.Our results show that Los treatment has a differential effect on the APCs populations in renal cortex and medulla, suggesting that renal APCs have different participations on hypertension according their microenvironment.Supported by Fondecyt #1201251 and #3201016