Feeding- and Light-Cycle Synergistically Regulate Mouse Blood Pressure Daily Rhythm via Bmal1 -Dependent and Independent Mechanisms

Abstract

Cardiovascular health requires the orchestration of the daily rhythm of blood pressure (BP), which responds to changes in light exposure and dietary patterns. Whether rhythmic light and feeding can modulate daily BP rhythm directly or via modulating intrinsic core clock gene Bmal1 is unknown. Using inducible global Bmal1 knockout mice (iBmal1KO), we explored the impact of rhythmic light, rhythmic feeding, or their combination on various physiological parameters. Daily rhythms of BP, heart rate, and locomotor activity were monitored via radiotelemetry, while food intake patterns were tracked using the BioDAQ system. Respiratory exchange ratio (RER) and energy expenditure (EE) were assessed through indirect calorimetry. In addition, spectrum analysis was employed to analyze spontaneous baroreflex sensitivity and heart rate variability, and urinary norepinephrine excretion was quantified using high-performance liquid chromatography (HPLC). Neither rhythmic feeding nor rhythmic light alone was sufficient to reinstate the daily BP rhythm in arrhythmic iBmal1KO mice. However, combining the light and feeding cues in synchrony partially restored the daily BP rhythm. Interestingly, rhythmic feeding alone robustly reinstated RER and EE rhythms, even without rhythmic light. Similar to BP, the partial reinstatement of the daily rhythms in heart rate and locomotor activity was observed only when rhythmic light and feeding were applied in tandem. Rhythmic light by itself did not restore the light–dark phase difference in baroreflex sensitivity, urinary norepinephrine excretion, or the daily rhythm of heart rate variability. However, rhythmic feeding, alone or in combination with rhythmic light, successfully reinstated the light–dark phase differences in these parameters. In the absence of Bmal1, the synergy between rhythmic light and feeding can partially restore daily BP rhythm.