Regulation of circadian blood pressure: from mice to astronauts

Abstract

Purpose of review: Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of blood pressure (BP) has been shown to be associated with greater target organ damage and with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP.

Recent findings: The time-keeper in mammals resides centrally in the suprachiasmatic nucleus. Apart from this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice with the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon three major factors: physical activity, autonomic function, and sodium sensitivity.

Summary: The integrated consideration of physical activity, autonomic function, and sodium sensitivity appears to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts.

Figure 1

Circadian variation in blood pressure, heart rate, and concomitant activity is shown for a patient with kidney disease. The horizontal lines are the median estimating statistic of rhythm (MESOR). The circular inset shows the time of peak effect (acrophase) on a 24 hour clock. Acrophases for both systolic and diastolic BP are seen during the hours of sleep. Acrophases for heart rate and activity are seen between noon and 6 PM. Activity units are arbitrary and taken as the square root of the average activity 5 minutes prior to each blood pressure measurement.

Figure 2

Factors that mediate dipping and conditions that impair dipping. The 3 factors that are primarily responsible for dipping are physical activity, sodium sensitivity and autonomic function. Impairments of any of these 3 functions can lead to non-dipping. Some conditions associated with non-dipping are shown outside these circles and discussed in the text. Diseases such as CKD are often associated with non-dipping the pathophysiology of which is complex and discussed in the text.