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Abstract: SA-PO777

Kidney Specific BMAL1 Knockout Reveal Differences in Circadian Rhythms of Blood Pressure Following a Low Potassium/High Salt Diet

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms

Authors

  • Drucker, Charles B., University of Florida College of Medicine, Gainesville, Florida, United States
  • Crislip, G. Ryan, University of Florida College of Medicine, Gainesville, Florida, United States
  • Costello, Hannah Mhairi, University of Florida College of Medicine, Gainesville, Florida, United States
  • Lynch, I. Jeanette, University of Florida College of Medicine, Gainesville, Florida, United States
  • Wingo, Charles S., University of Florida College of Medicine, Gainesville, Florida, United States
  • Gumz, Michelle L., University of Florida College of Medicine, Gainesville, Florida, United States
Background

Circadian rhythms are present in various physiologic functions, with irregularities being linked to cardiovascular disease, including hypertension, in humans. Previously, we have shown that knocking out the circadian clock factor BMAL1 in renal distal nephron and collecting duct cells of male mice (KS-BMAL1 KO) led to lower systolic blood pressure (SBP) than control mice (CNTL) with no effect on daily rhythms under a normal diet. Additionally, this effect was increased following a low potassium/high salt diet (0KHS; 4% NaCl). Our goal for this study was to determine if there were any genotype differences in circadian rhythms of SBP following a 0KHS diet.

Methods

SBP was measured via telemeter implants (N=7-8). KS-BMAL1 KO and CNTL were placed on a normal diet for 3 days, 0K diet for 7 days, and then a 0KHS diet for 10 days. Cosinor analysis on SBP was performed for each mouse during the last 3 days of normal and 0KHS diets to calculate mesor (midline estimating statistic of rhythm), amplitude (the extent of predictable change within a cycle), period (duration of a cycle from peak to peak), and acrophase (time at which the peak of a rhythm occurs). Two-way ANOVA with post-hoc analysis to compare between genotypes following 0KHS is provided.

Results

As expected, the mesor for SBP was lower in KS-BMAL1 KO compared to CNTL following 0KHS (p=0.0005). 0KHS increased mesor compared to normal diet. There were no differences between genotypes in the period. 0KHS diet also had no effect on SBP period. The period ranged from 23.0-24.9 hours. KS-BMAL1 KO had lower amplitude in SBP than CNTL following 0KHS (p=0.04). Additionally, 0KHS increased amplitude compared to normal diet in both groups (p<0.0001). There was no difference between genotypes in acrophase, however, 0KHS advanced the acrophase in both groups (p<0.0001).

Conclusion

Treatment with 0KHS affects rhythms of SBP by increasing the amplitude and advancing the acrophase, suggesting a role for diet in causing circadian disruption. BMAL1 within distal nephron and collecting duct cells contributes to SBP regulation following 0KHS and the amplitude of rhythms.

Funding

  • NIDDK Support