NLRP3 inhibitor MCC950 attenuated DOCA-salt-induced increases in blood pressure in male rats (190±1 vs 174±2 mmHg) but not female rats (167±4 vs 162±4 mmHg; Ptreatment=0.0033).
RCT
Does NLRP3 inhibition with MCC950 reduce blood pressure in male and female DOCA-salt hypertensive rats?
NLRP3 inhibition with MCC950 attenuates DOCA-salt-induced hypertension in male but not female rats, despite comparable increases in renal NLRP3 levels in both sexes.
p-value: p=0.0033
The immune system has been implicated in the development of hypertension and how the immune system is activated is of high interest. The NLRP3 inflammasome has been shown to contribute to the development of DOCA-salt hypertension in males, and we recently found that T cells contribute to sex differences in blood pressure with DOCA-salt. The first goal of the current study was to test the hypothesis that hypertensive males have greater NLRP3 expression than hypertensive females. We then tested the hypothesis that NLRP3 contributes to sex differences in DOCA-salt hypertension. NLRP3 was measured by ELISA in kidneys from hypertensive and normotensive men (n=6) and women (n=5) and from 11-week-old uninephrectomized (UNX) male and female Sprague Dawley (SD) following 3 wks of control or DOCA-salt treatment (n=5). Data were compared by 2-way ANOVA. To determine the impact of NLRP3 on blood pressure (BP), additional male and female DOCA rats were randomized to receive vehicle or the NLRP3 inhibitor MCC950 (10 mg/kg/day) and BP was measured by telemetry (n=5). Renal NLRP3 levels were comparable in normotensive men and women (ng/mg: 526±128 vs 723±134, Psex=0.78) and UNX control male and female rats (pg/mg: 45±4 vs 52±6, Psex=0.51). NLRP3 levels were higher in hypertensive men and women (ng/mg: 1522±303 vs 1441±117, PBP=0.0005) and DOCA-salt male and female rats (pg/mg: 92±9 vs 96±10, PBP< 0.0001) compared to normotensive controls, yet the increases were comparable between the sexes (Pinteraction=0.5 for humans and Pinteraction=0.85 for rats). DOCA-resulted in greater increases in BP in male rats vs females (Psex< 0.0001). Despite comparable increases in NLRP3 in male and female rats following 3 weeks of DOCA-salt treatment, treatment with MCC950 attenuated DOCA-salt-induced increases in BP in male (mmHg: 190±1 vs 174±2), but not female rats (mmHg: 167±4 vs 162±4; Ptreatment=0.0033, Pinteraction=0.04). The effectiveness of MCC950 was assessed by measuring renal NLPR3 mRNA expression at the end of the experiment. 3 weeks of MCC950 decreased NLRP3 in both sexes, although expression remained greater in males (Pinteraction=0.45, Ptreatment< 0.0001, Psex=0.0001). Together, these data support a role for the NLRP3 inflammasome to contribute to DOCA-salt induced in blood pressure, particularly in males. 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.
Sullivan et al. (Fri,) conducted a rct in Hypertension. MCC950 vs. Vehicle was evaluated on Blood pressure (p=0.0033). NLRP3 inhibitor MCC950 attenuated DOCA-salt-induced increases in blood pressure in male rats (190±1 vs 174±2 mmHg) but not female rats (167±4 vs 162±4 mmHg; Ptreatment=0.0033).