At1r blockade promotes transfer of hypertension by renal cd11c+f4/80+macrophages

Objective: The immune system participates in arterial hypertension (AHT) induced by Angiotensin II (AngII). dendritic cells (DCs)-CD11c+ and macrophages (Mo) are abundant in the kidney. However, new subpopulations of CD11c+ cells with Mo characteristics have been described, presenting an F4/80+ phenotype. Additionally, recent studies have shown a controversial role of the type 1 AngII receptor (AT1R) in CD11c+ cells. In this context, it is unknown whether Mo CD11c+-F4/80+ modifies their phenotype during AngII-induced inflammatory kidney damage, and whether this promotes AHT in an AT1R-dependent manner. The goal was evaluate whether renal Mo CD11c+-F4/80+ (rMo) modify their phenotype in AHT by AngII and determine whether their transfer to normotensive animals promotes AHT in an AT1R-dependent manner. Design and method: Male C57BI/6 mice (8 - 10 weeks, n = 6) were infused with AngII (490 ng/kg/min), AngII+Losartan (LOS; 20mg/kg/day, in drinking water), or vehicle for 14 -days. Systolic blood pressure (SBP) was measured by photoplestimography, DCs-CD11c+-F4/80- and rMo infiltrate were evaluated in cortex and medulla by flow cytometry. These cells were isolated and transferred to normotensive recipients, whose SBP was measured for 7-days (n = 3 - 5). Finally, the rMo were stimulated in vitro with AngII (100nM-24h) to analyze the abundance of mRNAs (Nox2, Sgk1, ENaC and AT1R; qRT-PCR). The data correspond to the mean ± standard deviation. Results: AngII increased SBP (AngII 134.7 ± 6.9 vs. Vehicle (Vh) 114.5 ± 7.8mmHg;p < 0.001) and promoted DCs-CD11c+F4/80- (AngII = 45.6 ± 11.9% vs. Vh = 31.7 ± 6.7%; p < 0.05) and Mo-CD11c+F4/80+ (AngII = 66.1 ± 8.4% vs. Vh = 55.6 ± 5.1%; p < 0.05) infiltration in renal medulla, and that was prevented by LOS (p < 0.05). We did not observe statistical differences in cortex. Interestingly, rMo transfer from AngII animals did not induce AHT in healthy recipient animals after 24h (Basal = 106.8 ± 2.3 vs.112.4 ± 4.9 mmHg;ns), compared to DCs-CD11c+-F4/80- (Basal = 110.0 ± 8.3 vs.132.0 ± 14.3mmHg;p < 0.05). However, the rMo of AngII+LOS animals increased SBP healthy recipients with respect to their baseline (basal = 109 ± 5.6 vs. 123 ± 8.0mmHg;p < 0.05). The rMo and DCs of hypertensive animals showed an increase in the abundance of AT1R (p < 0.05) compared to vehicle rMo. Conclusions: Pharmacological blockade of AT1R in vivo would have a differential effect on rMo, transferring AHT to normotensive animals. These findings suggest that subpopulations of renal CD11c+ cells have a differential role in AHT.