Long-term circadian disruption shortens lifespan and dampens blood pressure diurnal rhythms in stroke-prone spontaneously hypertensive rats.

Abstract

Environmental cues such as light and timing of food intake influence molecular clocks that produce circadian rhythmicity of many biological functions. The master circadian clock is entrained by light input and synchronizes to peripheral clocks in every organ. Careers that require rotating shift work schedules predispose workers to a constant desynchronization of biological clocks and are associated with increased risk of cardiovascular disease. We utilized a stroke-prone spontaneously hypertensive rat model exposed to a known biological desynchronizer, chronic environmental circadian disruption (ECD), and hypothesized that it would accelerate time to stroke onset. We investigated whether time-restricted feeding could delay stroke onset and evaluated its usefulness as a countermeasure when combined with the disruption of the light cycle. We found that a phase advancing schedule accelerated stroke onset. Restricting food access time to 5 hours/day regardless of lighting delayed stroke onset in both standard 12:12 light:dark or ECD lighting conditions compared with ad-lib feeding, but acceleration by ECD versus control lighting conditions was still observed. Since hypertension is a precursor to stroke in this model, we assessed blood pressure in a small cohort longitudinally using telemetry. Daily systolic and diastolic blood pressure was increased in both control and ECD conditions, thus hypertension was not accelerated to cause earlier strokes. We observed intermittent dampening of rhythms after each shift of the light cycle reminiscent of a relapsing-remitting non-dipping state. Our results suggest that constant ECD rhythms may be associated with increased risk of cardiovascular complications in the presence of cardiovascular risk factors.