Abstract 094: Bmal1 Is Necessary For Food-Based Entrainment Of Blood Pressure And Temperature Rhythms In The Rat

Abstract

Blood pressure (BP) follows a circadian rhythm, changing throughout the day. This change is crucial for cardiovascular health and in patient populations, as loss of these rhythms are associated with increased mortality and morbidity. Though BP rhythms have been recognized as important, the factors that control and entrain them are not well-described. Since the molecular clock is ubiquitously expressed in all cells and required for many circadian processes, we tested the hypothesis that the molecular clock contributes to the timing of BP rhythms in rats. Male and female rats with whole body loss of brain and muscle ARNTL-like protein ( Bmal1 ) and wild type (WT) controls (Sprague-Dawley background) were instrumented with telemeters in the abdominal aorta and placed in 12:12h light dark cycle (LD) to measure BP and core body temperature (TMP). Next, animals were placed in constant darkness (DD) for four weeks and then placed on a 12-hour time restricted feeding regimen (DD-TRF) for five days. Cosinor analysis was used to analyze BP and TMP rhythms. In a standard LD cycle, systolic BP (SBP) and TMP rhythms of both Bmal1 -knockout ( Bmal1- KO) and WT rats have similar amplitudes (2-way ANOVA for SBP and TMP, both p>0.05) which peak around zeitgeber time (ZT)18. During DD, WTs have SBP and TMP rhythms peak at circadian time (CT)19, while Bmal1 -KO rats have SBP and TMP rhythms that peak at CT 12. SBP amplitude is lower in all groups during DD compared to LD (WT males: 6.0±0.7 vs 3.8±0.7 mmHg; WT females: 7.2±0.9 vs 5.6±0.3 mmHg; KO males: 5.4±0.6 vs 4.7±0.4 mmHg; KO females: 6.2±0.6 vs 5.3±0.8 mmHg; 3-way ANOVA, p<0.05 for light cycle). During DD-TRF (CT 14.5 – 2.5), SBP and TMP rhythms of WTs peak at CT22. Bmal1 -KO rats have SBP and TMP rhythms that peak during CT16. SBP amplitude is lowered in Bmal1 -KO rats during DD-TRF compared to DD (KO males: 2.0±0.7 mmHg; KO females: 3.8±0.6 mmHg) but not in WT rats (WT males: 3.8±0.3 mmHg; WT females: 5.1±0.4 mmHg; 3-way ANOVA, p<0.05 for feeding time, sex, and feeding time*genotype). These data suggest that the molecular clock component Bmal1 is necessary for food-based entrainment of SBP and temperature rhythms in the absence of a regular light cue. Food, light cycle, and the molecular clock may all contribute to the timing and amplitude of SBP and TMP rhythms.