Long-term circadian disruption shortens life span and dampens blood pressure diurnal rhythms in stroke-prone spontaneously hypertensive rats.
Long-term circadian disruption shortens life span and dampens blood pressure diurnal rhythms in stroke-prone spontaneously hypertensive rats.
复制标题
长期昼夜节律紊乱会缩短易发生中风的自发性高血压大鼠的寿命并抑制血压昼夜节律。
DOI：
10.1152/ajpheart.00055.2023
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Davidson,AlecJ
中科院分区：
文献类型：
--
作者：
Ramsey,AnneM;Stowie,Adam;Hill,Atlantis;Ellis,Ivory;Rhodes,MeganK;Pollock,DavidM;Davidson,AlecJ
环境信号，如光线和食物摄入的时间，会影响分子时钟，从而产生许多生物功能的昼夜节律。主生物钟由光输入携带，并与身体每一个器官的外周时钟同步。需要轮班工作时间表的职业使员工容易使这些生物钟不断失去同步性，并与心血管疾病的风险增加相关。我们使用了一个易中风的自发性高血压大鼠模型，暴露于一种已知的生物去同步化因素--慢性环境昼夜节律中断(ECD)，以检验它将加速中风发病时间的假设。然后，我们调查了限时喂养是否可以延迟中风的发生，并评估了它作为一种对策的有效性，当它与光周期的持续中断相结合时。我们发现，轻度时程的相位提前加速了卒中的发生。与自由进食相比，标准12小时：12小时明/暗或ECD照明条件下，无论是标准的12小时：12小时亮/暗还是ECD照明条件下，无论是标准的12小时：12小时的明/暗还是ECD照明条件下，无论是在什么照明条件下，都将食物获取时间限制在5小时/天；然而，与对照照明条件相比，ECD的加速作用仍然被观察到。在这个模型中，由于高血压是中风的先兆，我们使用遥测技术对一小群人的血压进行了纵向评估。在对照组和ECD条件下的大鼠中，平均每天的收缩压和舒张压以类似的方式增加，因此高血压并没有严重加速导致更早的中风。然而，我们观察到在光周期的每一次转换后节律的间歇性抑制，这让人联想到复发-缓解的非浸泡状态。我们的结果表明，在存在心血管危险因素的情况下，环境节律的持续中断可能与心血管并发症的风险增加有关。
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 with peripheral clocks in every organ of the body. Careers that require rotating shift work schedules predispose workers to a constant desynchronization of these biological clocks and are associated with increased risk of cardiovascular disease. We used a stroke-prone spontaneously hypertensive rat model exposed to a known biological desynchronizer, chronic environmental circadian disruption (ECD), to test the hypothesis that it would accelerate the time to stroke onset. We then investigated whether time-restricted feeding could delay stroke onset and evaluated its usefulness as a countermeasure when combined with the constant disruption of the light cycle. We found that phase advancing of the light schedule accelerated stroke onset. Restricting food access time to 5 h/day regardless of lighting profoundly delayed stroke onset in both standard 12-h: 12-h light/dark or ECD-lighting conditions compared with ad libitum feeding; however, 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. Mean daily systolic and diastolic blood pressure increased in a similar manner across rats in control and ECD conditions, thus hypertension was not grossly accelerated to cause earlier strokes. However, we observed intermittent dampening of rhythms after each shift of the light cycle reminiscent of a relapsing-remitting nondipping state. Our results suggest that constant disruption of environmental rhythms may be associated with an increased risk of cardiovascular complications in the presence of cardiovascular risk factors.