Abstract: TH-PO326
A Role for the Adrenal Clock in Renin-Angiotensin-Aldosterone System Regulation
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
- Mckee, Annalisse Ray, University of Florida, Gainesville, Florida, United States
- Costello, Hannah Mhairi, University of Florida, Gainesville, Florida, United States
- Crislip, G. Ryan, University of Florida, Gainesville, Florida, United States
- Cheng, Kityan, University of Florida, Gainesville, Florida, United States
- Juffre, Alexandria, University of Florida, Gainesville, Florida, United States
- Mendez, Victor M., University of Florida, Gainesville, Florida, United States
- Douma, Lauren G., University of Florida, Gainesville, Florida, United States
- Gumz, Michelle L., University of Florida, Gainesville, Florida, United States
Background
Circadian rhythms are regulated by the circadian clock and critical for most physiological functions, with disruption of these rhythms linked to adverse renal outcomes. Our lab has a particular interest in the clock protein BMAL1 as global BMAL1 knockout (KO) mice have impairment of diurnal rhythm of renal sodium (Na) handing. Although, rhythm of renal Na handling in kidney-specific BMAL1 KO mice remained intact. The adrenal hormone, aldosterone, which is stimulated by the renin-angiotensin system (RAS), has an influence on renal electrolyte handing. With limited known on the role of the adrenal clock on RAS, aldosterone, and renal excretory function, our goal was to test the hypothesis that adrenal BMAL1 is required for normal circadian rhythms of RAS and renal Na excretion.
Methods
AS-BMAL1 male mice and littermate controls (n=5-6) were placed in metabolic cages to assess urinary 12-hour aldosterone excretion by ELISA and renal Na rhythm by flame photometry during normal Na diet and 7 days Na depletion. Kidneys were collected from a separate cohort of mice (n=7-8 per genotype) at 6AM and 6PM on normal salt diet for isolation of RNA and then qPCR to analyze gene expression for Renin.
Results
Here, we show urinary aldosterone levels were increased with blunted night/day difference in AS-BMAL1 KO male mice under normal salt and low salt conditions compared with controls (ANOVA interaction p=0.0407). Na balance was calculated, showing a trend for a significant interaction between genotype and time (p=0.05), appearing more positive during their inactive period. Finally, there was a significant interaction between time and genotype in Renin gene expression (ANOVA interaction p=0.0126).
Conclusion
In conclusion, loss of BMAL1 in the adrenal gland resulted in altered rhythm of both Renin gene expression and aldosterone levels, with a trend for significant disturbance in renal Na handling. Future studies aim to look at sex differences in the RAS system in AS-BMAL1 KO mice, as only males were investigated here.
Funding
- Private Foundation Support