Abstract 10254: Renal CD11c ⁺ F4/80 ^- Dendritic Cells, but Not Renal CD11c ⁺ F4/80 ⁺ Macrophages, Transfer the Hypertension From Angiotensin II-mice

Introduction: Immune system participates in Angiotensin II (AngII)-hypertension (HTN). Previously, it was shown that dendritic cells (DCs)-CD11c + are required for HTN development. However, new CD11c + cell subpopulations, presenting macrophages (Mφ) characteristics (F4/80 + ), have been described. Since renal DCs and Mφ share several markers, their participation in AngII-HTN remains under discussion. Our objective was to analyze whether renal DCs-CD11c + F4/80 - or/and CD11c + F4/80 + (Mφ) modify their phenotype in the AngII-HTN, and to determine if they promote HTN by transferring this phenotype to normotensive animals. Methods: Male C57BI/6 mice (8-10 weeks-old, n=6) were infused with AngII (490 ng/kg/min) by 14-days. We measured systolic blood pressure (SBP), and renal DCs-CD11c + F4/80 - and Mφ-CD11c + F4/80 + infiltrations were evaluated by flow cytometry. In addition, these cells were isolated at 14-days and transferred to normotensive mice (n=4-5) for SBP measurements. Finally, renal Mφ-CD11c + F4/80 + from HTN mice were stimulated in vitro with AngII (100nM-24h) to analyze the mRNAs abundance of Nox2 , Sgk1 , ENaC and AT 1 R , by qRT-PCR. Results: AngII increased SBP (AngII 134.7±6.9 vs. Vehicle (Vh) 114.5±7.8mmHg; p<0.001) and promoted the infiltration of DCs-CD11c + F4/80 - (AngII=45.6±11.9% vs. Vh=31.7±6.7%; p<0.05) and Mφ-CD11c + F4/80 + (AngII=66.1±8.4% vs. Vh=55.6±5.1%; p<0.05) in renal medulla. No statistical differences we observed in the renal cortex. Interestingly, the adoptive transfer of renal Mφ-CD11c + F4/80 + (1x10 6 -cells) from AngII animals to healthy recipient mice did not transfer HTN after 24h (baseline=106.8.0±2.3 vs. 112.4±4.5mmHg; ns), compared to DCs-CD11c + F4/80 - (baseline=110.0±8.3 vs. 132.0±14.3mmHg; p<0.05). Finally, renal Mφ-CD11c + -F4/80 + purified from HTN animals and re-stimulated in vitro with AngII did not show changes in the mRNA levels evaluated (p>0.05). Conclusions: The AngII-HTN promotes a differentiated infiltration of DCs-CD11c + F4/80 - and Mφ-CD11c + F4/80 + in renal medulla. However, only renal DCs, and not renal Mφ, acquire the ability to transfer HTN, suggesting that renal CD11c + cell subpopulations may have a differential role in AngII-HTN.Supported by Fondecyt-ANID #1201251 and #3201016