Scientific Reports · Nov 5, 2026
17β-estradiol increases diet-dependent salt retention in ovariectomized female mice
By Crislip GR, Lee R, Broderick B et al.
Circadian rhythms heavily influence blood pressure regulation. Genetic manipulation of core circadian clock genes alters blood pressure phenotypes. We have shown that male mice with renal distal segment knockout of the circadian transcription factor BMAL1 (kidney-specific cadherin Cre-positive BMAL1 knockout; KS-BMAL1 KO) exhibit lower blood pressure than wild-type controls, and this phenotype is exacerbated by a salt-sensitive diet. The BMAL1-dependent blood pressure phenotype in male KS-BMAL1 KO is absent in intact female mice. The current study aims to determine if estradiol modulates BMAL1-dependent blood pressure regulation in female mice. We hypothesized that ovariectomized (OVX) female mice would demonstrate a genotype difference in blood pressure and that estradiol would abolish this difference. OVX control and OVX KS-BMAL1 KO female mice subcutaneously received either a 17β‑estradiol pellet or placebo for three weeks prior to dietary treatment. Blood pressure was recorded daily via telemetric devices in OVX mice administered a baseline standard diet followed by 7 days of a low-K+ diet, then 7 days of a low-K+ high-salt diet. Contrary to our hypothesis, OVX mice with placebo pellets did not demonstrate a genotype difference in blood pressure. Furthermore, blood pressure between genotypes remained similar in OVX mice with an estradiol pellet. Estradiol supplementation led to higher mean arterial pressure by ~ 8 mmHg in both genotypes on a low-K+ high-salt diet. During the adaptation period to a low-K+ high-salt diet, OVX KS-BMAL1 KO mice have less sodium retention compared to OVX control mice and estradiol leads to more sodium retention compared to placebo. Under the conditions tested, there is no evidence that estradiol plays a role in BMAL1-dependent blood pressure regulation. These findings provide insight into the sex-specific role of BMAL1 in blood pressure regulation.