Bmal1 regulation of diurnal sodium and aldosterone excretion is sex dependent in the rat
Authors: Rhoads Megan , Pollock David 
Published: May 2023

Increasing evidence suggests the molecular clock is an important contributor to the maintenance of fluid-electrolyte balance. Our lab reported a loss of diurnal sodium excretion in male, but not female rats lacking the clock gene, Bmal1. Diurnal sodium excretion is maintained in both humans and rodents independent of typical timing cues including food intake. We recently reported that mice where food was restricted to the light period, inactive time restricted feeding (iTRF) maintained elevated aldosterone excretion. Thus, we hypothesized that Bmal1 maintains diurnal rhythms of aldosterone and electrolyte excretion during mistimed food intake. Male and female Bmal1-KO rats and littermate controls in 12:12 light:dark on standard 0.49% NaCl diet in metabolic cages to facilitate 12h urine collection. Following baseline measurements, food was restricted to the 12h light period for 5 days (iTRF). 12h urine samples were collected for the final 2 days. During ad libitum feeding, male WT and KO rats excreted more aldosterone (ELISA) at night compared to the day (WT: 2.4±0.5 vs. 1.3±0.2 ng/12 hrs; KO: 2.3±0.6 vs. 1.0±0.1 ng/12hrs, night vs. day; p<0.05 for time of day, all analysis by 3-way ANOVA). During ad libitum feeding, male WT rats excrete more sodium at night compared to the day, but male KO rats did not display a diurnal rhythm for sodium excretion (WT: 0.89±0.1 vs. 0.57±0.07 mmol/12 hrs; KO: 0.62±0.07 vs. 0.56±0.09 mmol/12hrs, night vs. day; p<0.05 for WT). During iTRF, KO males had elevated aldosterone excretion at night, but WT males did not (WT: 1.1±0.1 vs. 1.3±0.3 ng/12 hrs; KO: 2.1±0.2 vs. 1.5±0.2 ng/12hrs, night vs. day; p<0.05 for TOD). During iTRF, diurnal sodium excretion was not evident in either genotype (WT: 0.42±0.08 vs. 0.42±0.07 mmol/12 hrs; KO: 0.49±0.06 vs. 0.75±0.1 mmol/12hrs, night vs. day). Female WT and KO rats both displayed diurnal patterns in aldosterone excretion during ad libitum feeding (WT: 2.1±0.7 vs. 1.1±0.1 ng/12 hrs; KO: 2.5±0.3 vs. 1.3±0.1 ng/12hrs. night vs. day; p<0.05 for time of day✕time of feeding). During ad libitum feeding, female WT rats have a diurnal difference in sodium excretion, but female KO rats do not (WT: 0.91±0.04 vs. 0.61±0.05 mmol/12 hrs; KO: 0.6±0.07 vs. 0.54±0.04 mmol/12hrs, night vs. day; p<0.05 for WT). During iTRF, both WT and KO females lost diurnal differences in aldosterone, but KO females had elevated aldosterone excretion (WT: 1.3±0.3 vs. 1.5±0.4 ng/12 hrs; KO: 2.1±0.4 vs. 2.5±0.5 ng/12hrs, night vs. day; p<0.05 for time of day✕time of feeding). During iTRF, WT females had similar sodium excretion between night and day, but KO females had an inverted sodium excretion pattern (WT: 0.5±0.03 vs. 0.37±0.05 mmol/12 hrs; KO: 0.23±0.03 vs. 0.55±0.05 mmol/12hrs, night vs. day; p<0.05 for KO). These data support a role for Bmal1 in regulating diurnal aldosterone excretion in a sex dependent manner. Supported by AHA Postdoctoral grant 827566 to MKR and NIH NHLBI P01 to DMP. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.