Abstract Body: T cells contribute to the development of hypertension, but what mediates T cell activation in hypertension is still being investigated. The NLRP3 inflammasome is a key mediator of the inflammatory response, and NLRP3 contributes to deoxycorticosterone acetate (DOCA)-salt hypertension in male mice. Little is known regarding the role of NLRP3 in hypertensive females, but we previously published that greater increases in blood pressure (BP) in male DOCA-salt rats vs females is associated with a more pro-inflammatory T cell profile. The goal of the current study was to test the hypothesis that greater NLRP3 activation in males contributes to greater increases in BP and a more pro-inflammatory T cell profile than in females. METHODS: Initial studies measured NLRP3 and IL1-β mRNA expression in kidneys of uninephrectomized (UNX) male and female Sprague Dawley rats randomized to vehicle or DOCA treatment (n=5/group). Additional UNX male and female rats were randomized to DOCA plus vehicle or an NLRP3 inhibitor, MCC950 (10 mg/kg), for 3 weeks. BP was measured via telemetry (n=5/group). Kidneys were harvested for flow cytometric analysis of T cells. Data were compared via 2-way ANOVA. RESULTS: DOCA increased renal NLRP3 and IL1-β mRNA in males and females (NLRP3: P_treatment<0.0001, P_sex=0.0014; IL1-β: P_treatment<0.0001, P_sex=0.05), and increases were greater in males (P_interaction=0.04, P_interaction=0.02, respectively). DOCA treatment increased BP in males (105±4 to 190±1 mmHg) and females (97±3 to 167±5 mmHg), and treatment with MCC950 attenuated DOCA-induced increases in BP in both sexes (males: 107±3 to 174±2 mmHg; females: 98±3 to 159±7 mmHg; P_treatment=0.004). Terminal BP values were compared and while BP was higher in males, the impact of MCC950 was comparable between the sexes (P_sex=0.0001; P_interaction=0.4). However, MCC950 attenuated DOCA-induced increases in renal CD4₊ T cells and Th17 cells to a greater degree in males than in females (CD4+: P_treatment<0.001, P_sex=0.03, P_interaction=0.04; Th17 cells: P_treatment<0.001, P_sex=0.001, P_interaction=0.04). CONCLUSIONS: NLRP3 contributes to the development of DOCA-salt induced increases in BP and inflammation in both males and females. However, males have greater NLRP3-mediated increases in renal T cells than females. The impact of this mechanism on renal function and the potential for targeted hypertensive therapies needs to be further examined.