Abstract P167: Chronic Circadian Disruption Impairs Cardiovascular Rhythms In Mice

Abstract

Shift workers have an increased risk of developing hypertension and higher incidence of metabolic syndrome. Circadian rhythm disruption increases cardiometabolic disease risk in humans and animals. We hypothesized that chronic circadian disruption (CCD) disrupts blood pressure, heart rate, and locomotor activity rhythms. Male 8-week old C57BL/6J mice were under a standard light/dark cycle (12-h light, 12-h dark, control) or a CCD protocol (10-h light, 10-h dark, T20) with ad libitum food and water for 10 weeks. T20 mice gained significantly more body weight (n=6, p=0.04; time: p<0.001, light cycle: p<0.001). Mean arterial pressure (MAP), heart rate (HR), and locomotor activity were measured by telemetry after 10 weeks of CCD. Average MAP, HR, and activity were calculated during light and dark periods. MAP between the light and dark periods was significantly different in control mice (12:12 LD), while T20 mice (10:10 LD) did not show diurnal variation (Control 119±3 mm Hg vs.101±2 mm Hg, dark vs. light, respectively, p<0.001; T20 114±13 mm Hg vs.113±12 mm Hg, dark vs. light, respectively, p=0.86; n=3-4 in all groups). Control mice showed a diurnal variation in HR, whereas T20 mice did not show a light-dark difference (Control 584±11 bpm Hg vs. 511±4 bpm, dark vs. light, respectively, p=0.001; T20 537±14 bpm vs. 526±5 bpm, dark vs. light, respectively, p=0.48; n=3-4 in all groups). Dark phase HR was significantly decreased in T20 mice (p=0.01, control dark vs. T20 dark). Control mice showed a light-dark difference in activity, while T20 mice lacked diurnal variation in the activity rhythm (Control 9.6±1.3 counts/min Hg vs. 3.1±0.3 counts/min, dark vs. light, respectively, p<0.001; T20 6.9±0.3 counts/min vs. 6.0±0.8 counts/min, dark vs. light, respectively, p=0.92; n=3-4 in all groups). T20 mice also displayed significantly higher activity during the light phase (p=0.04, control light vs. T20 light). Time of day and the interaction between time of day and light cycle, respectively, were significant between control and T20 mice for MAP, HR, and activity (n=3-4, MAP: p=0.001 and p=0.002; HR: p=0.001 and p=0.004; Activity: p=0.001 and p=0.004). These results indicate that CCD impairs cardiovascular and behavioral rhythms, which may lead to cardiovascular disease.