Abstract P313: Chronic Circadian Disruption Impairs Blood Pressure Rhythm And Leads To Vascular Disease In Mice

Abstract

Shift workers have an elevated risk of developing hypertension and higher incidence of cardiovascular disease. Circadian rhythm disruption increases cardiometabolic disease risk in both humans and animals. We hypothesized that chronic circadian disruption (CCD) impairs cardiovascular rhythms and leads to vascular disease. Male 8-week old C57BL/6J mice were subjected to 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 wks. T20 mice had an increased rate of weight gain (n=6, p=0.04; time: p<0.001, light cycle: p<0.001). Mean arterial pressure (MAP), heart rate (HR), and activity were measured by telemetry after 10 weeks of CCD. Control mice (12:12 LD) had significant diurnal variation in MAP, while T20 mice (10:10 LD) lacked diurnal variation (control 119±3 vs.101±2 mm Hg, dark vs. light, p<0.001; T20 114±13 vs.113±12 mm Hg, dark vs. light, p=0.86; n=3-4). Control mice had a diurnal variation in HR which was absent in T20 mice (Control 584±11 vs. 511±4 bpm, dark vs. light, p=0.001; T20- 537±14 vs. 526±5 bpm, dark vs. light, p=0.48; n=3-4). Dark phase HR was significantly lower in T20 mice (p=0.01, control vs. T20). Control mice had a light-dark difference in activity, while T20 mice lacked diurnal variation in activity with significantly higher light phase activity (p=0.04, control vs. T20). Aortic pulse wave velocity (PWV), a measure of vascular stiffness, was significantly higher after 6 weeks in T20 mice compared to control mice (Control: 1.60±0.1 m/s; T20: 2.25±0.1 m/s; n=6, p=0.0037), although aortic wall thickness was similar between groups. Wire myography in isolated aortic rings was used to assess vascular reactivity with cumulative concentration responses to phenylephrine (PE) and acetylcholine (ACh). CCD reduced sensitivity (EC50) to PE-induced vasoconstriction (Control: -6.92±0.06 M; T20: -6.74±0.04 M, n=6, p=0.03), while there were no significant changes seen in the ACh sensitivity or maximal response. These data show that CCD impairs cardiovascular and behavioral rhythms linked to the development of aortic stiffness.