Abstract P1127: Reverse Feeding Abolishes Circadian Blood Pressure Rhythms in Bmal1-Knockout Rats

Abstract

Blood pressure follows a strong circadian rhythm regulated by the molecular clock, which can be entrained by light, feeding, and other cues. Using a whole body knockout of a central clock gene, Bmal1 (Bmal1KO), we tested the hypothesis that food availability would entrain circadian blood pressure rhythms with a functional molecular clock. Male and female rats were implanted with a telemetry transmitter to measure 24-hour mean arterial pressure (MAP). Following recovery, rats were placed in metabolic cages to measure food and water intake. Rats were allowed ad lib access to food for three days and then food was restricted to the inactive period (lights on, 7 am to 7 pm) for five days. Under ad lib feeding conditions, male littermate control rats (n=8) had a MAP of 113.3±2.6 mmHg during the inactive period and a significantly higher MAP during the active period (120.6±3.1 mmHg, repeated measures ANOVA with Sidak’s post hoc, p<0.0001). Similarly, Bmal1KO rats (n=12) had a significantly higher MAP during the active period (114.5±1.8 mmHg) versus the inactive period (108.9±2.0 mmHg, p<0.0001). Under reverse feeding conditions, control rats had an average MAP of 118.3±2.5 mmHg during the inactive period and a significantly higher MAP to 121.7±2.8 mmHg during the active period (p<0.0001). Bmal1KO rats had similar MAPs during the inactive and active periods (113.1±1.7 vs. 113.3±1.8 mmHg, respectively, p=0.99). During ad lib feeding, female control rats (n=7) had a significant diurnal pattern with an average MAP of 110.6±1.4 mmHg in the inactive period and 118.9±1.9 mmHg during the active period (p<0.0001). Female Bmal1KO rats (n=3) had an average MAP of 104.7±0.4 mmHg in the inactive period and a significantly higher MAP of 110.5±0.3 mmHg during the active period (p<0.001). Under reverse feeding conditions, female control animals maintained a significant diurnal MAP from inactive to active periods (110.6±1.5 vs. 115.3±1.9 mmHg, respectively, p<0.0001), but female Bmal1KO animals had no significant difference in inactive and active period MAP (105.0±0.3 vs. 106.8±0.4 mmHg, respectively, p<0.0001). Together, these data suggest that food availability contributes to the circadian blood pressure rhythms in male and female Bmal1 knockout rats.