Abstract 005: Renal Macrophages From Losartan Treated Mice Transfer The Hypertension

The immune system participates in the Angiotensin II (AngII)-dependent hypertension (HTN). Dendritic Cells (DCs)-CD11c + and macrophages (Mo) are abundant in the kidney. However, new subpopulations of CD11c + cells with Mo characteristics (F4/80 + ) have been described. Recently, studies have shown that type-1 AngII receptor (AT 1 R) in CD11c + cells could have a protective effect on HTN in contrast to the pro-hypertensive effects of AT 1 R activation in other cells. Here, our goal was to evaluate whether renal Mo (rMo) modify their phenotype during AngII-induced inflammatory kidney damage, and whether their transfer to normotensive animals promotes HTN in an AT 1 R-dependent manner. Male C57BI/6 mice (10 weeks, n=6) were infused with AngII (490 ng/kg/min), AngII+Losartan (LOS; 20mg/kg/d, in drinking water), or vehicle (Vh) for 14-days. Systolic blood pressure (SBP) was measured by plethysmography. Renal DCs (rDCs, CD11c + F4/80 - ) and rMo (CD11c + F4/80 + ) were evaluated by flow cytometry and isolated at 14-days for the transfer to normotensive mice, which were followed for 7-days (n=4-5). Finally, rDCs and rMo were stimulated in vitro with AngII (100nM, 24h) to analyze the mRNAs abundance of AT 1 R. All data are presented by mean±standard deviation.LOS prevented the SBP rise (AngII+LOS=110.3±11.1 vs. AngII=134.7±6.9 mmHg; p<0.01) and the increase of rDCs population (AngII+LOS=12.8±2.0% vs. AngII=16.5±0.6%; p<0.01) induced by AngII, without changing rMo population. The rMo transfer from AngII mice did not induce HTN in normotensive animals after 24h (basal=106.8±2.3 vs. 112.4±4.9 mmHg; ns), compared to rDCs (Basal=110.0±8.3 vs. 132.0±14.3 mmHg; p<0.05). However, the rMo from AngII+LOS mice increased SBP in healthy animals compared to their baseline (basal=109±5.6 vs. 123±8.0 mmHg; p<0.05). This effect was not observed by rDCs transfer (basal=109±2.9 vs. 113±7.0 mmHg; ns). Finally, the rMo from AngII mice showed an increase in the AT 1 R mRNA abundance (p<0.05), compared to Vh rMo, however, AngII in vitro treatment did not modify the mRNA levels.The in vivo AT 1 R antagonism may have a differential effect on rMo, transferring HTN to normotensive mice. These findings suggest that subpopulations of renal CD11c + cells have a differential role in HTN.Fondecyt 1231909