Circadian clock-mediated regulation of blood pressure

Abstract

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.

Keywords: Blood pressure; Circadian rhythm; Humans; Hypertension; Mouse; Non-dipping.

Figure 1. Molecular circadian clocks throughout the body contribute to the circadian rhythm of blood pressure

Studies with rodents and humans suggest that clock components within the kidneys, brain, nervous system, heart, and vasculature all contribute to the regulation of the BP circadian cycle. The molecular circadian clock within these tissues regulates the physiological functions that contribute to overall BP regulation. BP has a 24-hour cycle, with a peak in BP during the day and a 10-20% dip in BP at night. Dysregulation of the BP circadian rhythm can have profound effects, including a greater risk of stroke and cardiovascular disease.