Angiotensin II infusion increased day 14 renal inflammatory monocytes more in males than females (6.7% vs 0.6%, p<0.05), paralleling sustained hypertension in males but not females.
Sex-dependent immune kinetics in the kidney, with males showing pro-inflammatory activation and females showing a tolerogenic shift, may contribute to differential blood pressure regulation during AngII-induced hypertension.
Sex differences influence hypertension, as premenopausal females are protected from angiotensin II (AngII) induced blood pressure elevation, tissue injury, and inflammation. We hypothesized that AngII induces time-dependent and subset-specific increases in renal innate immune cells with distinct kinetic patterns between sexes. This study aimed to characterize the timeline of renal innate immune cell infiltration in males and premenopausal females during AngII-induced hypertension. Male and female 10-week-old C57BL/6J mice were infused with AngII (800 ng/kg/min) via osmotic mini-pumps. Systolic blood pressure was taken via tail cuff and DSBP was calculated. Kidneys were harvested at 3, 7, and 14 days, and single-cell suspensions were analyzed by multicolor flow cytometry to quantify major renal innate immune populations, including macrophages, inflammatory monocytes, neutrophils, and dendritic cell subsets (cDC1s, cDC2s, and MoDCs). Macrophage polarization (M1/M2) was also assessed. Absolute counts and frequencies were calculated. In females DSBP at day 3 (d3) AngII was 13.9 mmHg, at d7, 12.0 mmHg and d12, 4.4 mmHg. In males DSBP at d3 Ang II was 8.1 mmHg, d6, 20.3 mmHg and d13, 24.8 mmHg. Males had more renal infiltration of neutrophils compared to females following Ang II (d3 Control Male: 2.1 ± 1.5%; Male AngII: 8.4 ± 2.1% vs Control Female: 0.9 ± 0.08%; Female AngII: 1.8 ± 0.1% p< 0.05). Females had significantly higher renal F4/80+ macrophages (d3 F: 27.9 ± 2.9% vs M:17.2 ± 3.0%, p< 0.05) and MoDCs (d3 F:34.2 ± 0.9% vs M:18.6 ± 2.1%, p< 0.05) than males throughout the study. By d7, inflammatory monocytes remained elevated in males versus females (M:5.0 ± 0.5% vs. F:3.4 ± 0.4%, p< 0.05), while females had higher M2 macrophages (F:1.8 ± 0.1% vs. M:0.2 ± 0.05%, p< 0.05) and MoDCs (F:53.2 ± 8.0% vs. M:7.1 ± 0.8%, p< 0.05). At day 14, males showed higher inflammatory monocytes (M:6.7 ± 0.6% vs. F:0.6 ± 0.1%, p< 0.05), cDC2s (M19.7 ± 1.5% vs. F5.3 ± 0.1%, p< 0.05), and inflammatory cDC2s (p< 0.05) compared to females. Females maintained higher frequencies of M2 macrophages and MoDCs compared to males at d14, despite reductions in F4/80+ macrophages and classical dendritic cells (p< 0.05). This study demonstrates that AngII drives different renal innate immune patterns in males and females that align with blood pressure kinetics. In males, persistent pro-inflammatory innate immune activation parallels sustained hypertension, whereas females exhibit a tolerogenic immune shift towards M2 polarization and MoDC expansion that coincides with a prevention of hypertension. These findings suggest that sex-dependent immune kinetics in the kidney may contribute to differential blood pressure regulation during AngII-induced hypertension. This project is funded by U2C DK133422 & TL1 DK139566 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Delaune et al. (Fri,) conducted a other in Angiotensin II-induced hypertension. Angiotensin II vs. Control was evaluated on Renal innate immune cell infiltration and blood pressure kinetics. Angiotensin II infusion increased day 14 renal inflammatory monocytes more in males than females (6.7% vs 0.6%, p<0.05), paralleling sustained hypertension in males but not females.