BMAL1 in Renal Distal Segments Does Not Contribute to Variations in Beat‐to‐Beat Blood Pressure but a Low Potassium Diet Increases Blood Pressure Variability

Abstract

IntroductionBlood pressure (BP) regulation is a dynamic process. Beat‐to‐beat fluctuations in BP can be studied by frequency domain analysis to determine variability. Measurements of BP and the heart rate variability have been used as an indication of cardiovascular health and autonomic nervous system (ANS) activity. The circadian clock, which is comprised of four core transcriptional factors, including BMAL1, regulates a variety of physiological and autonomic functions in the body such as BP and heart rate. Previously, we generated renal distal segment specific BMAL1 male knockout mice (dsBMAL1 KO) that exhibit lower BP compared to control mice (CNTL).GoalThe goal of this study was to determine if BMAL1 knockout within the distal segments of the kidney affects BP variability before or after dietary potassium depletion.MethodsMale 14–18‐week‐old mice were implanted with telemeter devices. Following recovery, basal mean arterial pressure and heart rate were measured. Data was collected at 1000 Hz for 2 minutes every hour during the active period (ZT 12–20) and inactive (ZT 0–8) period. Following basal measures, mice were given low potassium diet for 5 days. Data are from the active period of the 5th day (ZT 12–16). Fourier analysis was performed via Kubios software using pre‐determined high‐frequency (HF) and low‐frequency (LF) scaling established for mice. Data were analyzed by 2‐way ANOVA to test for time and genotype effects at baseline, and for genotype and treatment to assess effect of dietary potassium depletion. N=7 CNTL and 8 renal dsBMAL1 KO.ResultsAs expected, mean heart rate was higher during the active period vs. inactive (CNTL: 613 ± 12.7 vs. 508 ± 13.7 bpm; dsBMAL1 KO: 661 ± 17.0 vs. 538 ± 11.7 bpm; PTIME<0.0001), furthermore, dsBMAL1 KO exhibited faster heart rates than CNTL (PGENOTYPE<0.05). Power spectral analysis of mean arterial pressure indicated that there was greater variability during the inactive period vs. active in HF bands (PTIME<0.0001) but no genotype differences were found. Additionally, spectral analysis did not demonstrate any significant differences in the ratio of LF/HF regardless of active period or genotype (PTIME=0.4; PGENOTYPE=0.3). Nighttime (ZT 12–16) HF BP variability was higher following potassium depletion compared to baseline (CNTL: 8.25 ± 0.199 vs. 8.97 ± 0.079 mmHg2/Hz; dsBMAL1 KO: 8.63 ± 0.170 vs. 9.07 ± 0.279 mmHg2/Hz; PTREATMENT<0.01).ConclusionsBMAL1 in renal distal segments does not contribute to variations in beat‐to‐beat BP. Renal dsBMAL1 KO exhibit a faster heart rate independent of variability. Potassium depletion increases BP variability in this experimental setting. Using this analysis software, changes in BP variability reflected changes in heart rate with faster heart rates correlating with less BP variability.Support or Funding InformationNIH/NIDDK 1R01DK109570‐01A1 (PI: Gumz), Gatorade Trust through the UF Department of Medicine, 19POST34450134 AHA Postdoc Fellowship, North Florida/South Georgia Veterans Health Systems