Female Sex Hormones Protect Against Salt‐Induced Increases in Immune System Activation in Dahl Salt‐Sensitive Rats (DSS)

T cells contribute to hypertension and renal injury in response to a high‐salt (HS) diet in male DSS. This study tested the hypotheses that 1) salt increases renal T cell infiltration in female DSS and 2) sex hormones protect against the pro‐inflammatory effects of salt. Female DSS were randomized to the following groups: gonad‐intact + normal‐salt (NS), ovariectomized (OVX) + NS, intact + 4% HS, OVX + HS for 2 weeks (n=3/group). Blood pressure (BP) was measured by telemetry, protein excretion was measured weekly and kidneys were processed for flow cytometric analysis of T cells and high mobility group box 1 protein (HMGB1), HMGB1 is released by damaged cells and stimulates pro‐inflammatory T cells. OVX exacerbated HS‐induced increases in BP and protein excretion (32% increase and 122% increase, respectively) compared to intact DSS (22% increase and 80% increase; p<0.05). OVX and HS increased pro‐inflammatory renal CD4+ T cells (p<0.05) and Th17 cells (p<0.05) and decreased immuno‐suppressive T regulatory cells (Tregs; p<0.001), however, HS induced a greater increase in CD4+ T cells in OVX vs. intact (p<0.001) and a greater decrease in Tregs in intact vs. OVX DSS (p<0.001). Renal HMGB1 increased with HS (p<0.01) and OVX (p<0.001), although the increase was greater in OVX vs. intact DSS (p=0.03). In summary, OVX DSS have the greatest increase in T cells and HMGB1 as well as the highest BP and proteinuria. We propose that female sex hormones protect against the pro‐inflammatory effects of a HS diet by mitigating the release of HMGB1.CD4 + cells (expressed as %CD3 + cells) Th17 cells (expressed as %CD3 + CD4 + cells) Tregs (expressed as %CD3 + CD4 + cells) HMGB1 (expressed as % total kidney cells)Intact NS 25±0.6 8±0.6 9±0.3 2±0.3Intact HS 29±0.3 10±0.6 5±0.6 4±0.6OVX NS 29±0.3 14±1.0 2±0.3 5±0.6OVX HS 40±0.7 17±1.0 1±0.3 9±0.6