Department of Medicine, Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, FL 32610, United States; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, United States.
Department of Medicine, Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, FL 32610, United States; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, United States.
Free Radic Biol Med. 2018 May 1;119:108-114. doi: 10.1016/j.freeradbiomed.2017.11.024. Epub 2017 Dec 2.
Most bodily functions vary over the course of a 24h day. Circadian rhythms in body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) are just a few examples. These circadian rhythms are controlled by the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks located throughout the body. Light and food cues entrain these clocks to the time of day and this synchronicity contributes to the regulation of a variety of physiological processes with effects on overall health. The kidney, brain, nervous system, vasculature, and heart have been identified through the use of mouse models and clinical trials as peripheral clock regulators of BP. The dysregulation of this circadian pattern of BP, with or without hypertension, is associated with increased risk for cardiovascular disease. The mechanism of this dysregulation is unknown and is a growing area of research. In this review, we highlight research of human and mouse circadian models that has provided insight into the roles of these molecular clocks and their effects on physiological functions. Additional tissue-specific studies of the molecular clock mechanism are needed, as well as clinical studies including more diverse populations (different races, female patients, etc.), which will be critical to fully understand the mechanism of circadian regulation of BP. Understanding how these molecular clocks regulate the circadian rhythm of BP is critical in the treatment of circadian BP dysregulation and hypertension.
大多数身体机能在 24 小时的周期内发生变化。体温、睡眠-觉醒周期、新陈代谢和血压(BP)的昼夜节律只是其中的几个例子。这些昼夜节律受下丘脑视交叉上核(SCN)中的中央时钟和全身各处的外周时钟控制。光和食物提示使这些时钟与一天中的时间同步,这种同步有助于调节各种生理过程,对整体健康产生影响。通过使用小鼠模型和临床试验,已经确定肾脏、大脑、神经系统、血管和心脏是 BP 的外周时钟调节器官。BP 的这种昼夜节律失调(无论是否伴有高血压)与心血管疾病风险增加有关。这种节律失调的机制尚不清楚,这是一个正在不断发展的研究领域。在这篇综述中,我们强调了人类和小鼠昼夜节律模型的研究,这些研究提供了对这些分子钟及其对生理功能影响的深入了解。需要进行更多针对特定组织的分子时钟机制研究,以及包括更多不同人群(不同种族、女性患者等)的临床研究,这对于全面了解 BP 昼夜节律调节的机制至关重要。了解这些分子钟如何调节 BP 的昼夜节律对于治疗昼夜节律性 BP 失调和高血压至关重要。