Abstract: TH-PO328
Assessment of Sodium Excretion in Kidney-Specific BMAL1 Knockout Mice in Response to an Acute Salt Load
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders
- 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic
Authors
- Crislip, G. Ryan, University of Florida, Gainesville, Florida, United States
- Costello, Hannah Mhairi, University of Florida, Gainesville, Florida, United States
- Cheng, Kityan, University of Florida, Gainesville, Florida, United States
- Drucker, Charles B., University of Florida, Gainesville, Florida, United States
- Lynch, I. Jeanette, University of Florida, Gainesville, Florida, United States
- Douma, Lauren G., University of Florida, Gainesville, Florida, United States
- Wingo, Charles S., University of Florida, Gainesville, Florida, United States
- Gumz, Michelle L., University of Florida, Gainesville, Florida, United States
Background
BMAL1 is a core clock transcription factor responsible for the tissue-specific regulation of thousands of genes. Male kidney-specific BMAL1 knockout (KS-BMAL1 KO) mice exhibit lower blood pressure compared to control mice (CNTL). The goal of this study was to determine the natriuretic response to an acute salt load in the presence and absence of the sodium-potassium-chloride-cotransporter 2 (NKCC2) by inhibition with furosemide in KS-BMAL1 KO and control mice (CNTL).
Methods
We generated the KS-BMAL1 KO using floxed exon 8 BMAL1 mice crossed with kidney-specific cadherin Cre+ mice. These mice exhibit decreased BMAL1 expression in the thick ascending limb, distal convoluted tubule, and collecting duct cells. Floxed Cre- littermates were used as control mice (CNTL). Mice were placed in metabolic cages and fasted during their inactive period (N=6). At the start of their active period, mice were injected with a saline bolus (1.5 mL) ± furosemide (30 mg/kg). Urine was collected for each hour for 7 hours. Three- and two-way ANOVA were used for statistical analysis.
Results
There was no genotype difference in cumulative sodium excretion. Mice injected with furosemide excreted more sodium compared to saline alone (final volume in saline alone vs. furosemide; CNTL: 0.14±0.01 vs. 0.22±0.02; KS-BMAL1 KO: 0.14±0.02 vs. 0.25±0.01 mEq; P<0.0001). Cumulative urinary volume exhibited the same trends. Likewise, cumulative sodium excretion rates were similar between genotypes and furosemide caused faster excretion over the course of collections.
Conclusion
BMAL1 does not appear to control NKCC2 activity under the conditions tested. As expected, furosemide leads to greater and quicker diuresis and natriuresis. We have shown that blood pressures difference between CNTL and KS-BMAL1 KO is amplified following potassium depletion with high salt diet. Assessing natriuresis in response to an acute salt load in mice fed a potassium depleted, high salt diet may provide additioal insight.
Funding
- NIDDK Support