Female Mice are Protected From Angiotensin II-Induced Changes in Renal Function

Premenopausal female mice are protected from angiotensin II (ANG II) induced hypertension compared to males. However, in post-menopausal females this protection is lost and ANG-II infusion induces hypertension and an associated pro-inflammatory response in the kidney, suggesting a protective role for estrogen in modulating the immune response. Changes in renal function and lower renal sodium excretion are causal for the development of ANG II-induced hypertension. However, studies to directly compare sex differences in the progression of ANG II-induced hypertension, glomerular filtration rate (GFR), and renal sodium transport have been limited. We hypothesized that in contrast to males, females are protected against ANG II-induced hypertension via their ability to maintain sodium excretion in the face of ANG II infusion. 12-week-old male and female C57BL/6 mice were infused with ANG II (800ng/kg/day) via osmotic minipump. Systolic blood pressure (SBP) was measured via tail cuff. GFR was measured transdermally (medibeacon). To evaluate natriuretic capacity, saline challenges were performed. There was a similar increase in SBP in males and females following ANG II infusion until day 5. However, on day 6, ANG II-infused male mice had a greater increase in SBP, and SBP continued rising (day 13 male ANG II: ∆25 ± 7 mmHg, *p≤0.05 vs control). In contrast, female mice did not show a further increase in SBP after day 6 (day 12 female ANG II ∆3 ± 5 mmHg, ns vs control). From day 6 onwards GFR was significantly reduced in ANG II infused male mice (day 13 male ANG II: ∆ -70 µL/min *p≤0.05 vs control males); however, ANG II infusion did not modify GFR in female mice. At day 13 ANG II infused male mice had a significant reduction in diuresis following a saline challenge (male control 1.3 ± 0.2 mL vs male ANG II 0.6 ± 0.1 mL, *p≤0.05), however female ANG II infused mice had no significant reduction in diuresis (female control 1.1 ± 0.1 ml vs female ANG II 1.2 ± 0.2 ml). The data suggest that protection from ANG II-induced hypertension in female mice is due to preserved GFR and natriuresis. The protection of the female kidney correlated with an absence of an inflammatory phenotype. This project is funded by R01NS110749 and R01DK083785. This abstract was presented at the American Physiology Summit 2025 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.