Regulation of circadian blood pressure: from mice to astronauts.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Nephrology, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana 46202, USA. ragarwal@iupui.edu
Rajiv
R
Agarwal
D000818:Animals; D018480:Astronauts; D001341:Autonomic Nervous System / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology; D024821:Metabolic Syndrome / Q000503:physiopathology; D051379:Mice; D008955:Models, Cardiovascular; D009043:Motor Activity / Q000502:physiology; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology / Q000628:therapy; D012891:Sleep Apnea Syndromes / Q000503:physiopathology; D012982:Sodium, Dietary / Q000008:administration & dosage; D013026:Space Flight
D012982:Sodium, Dietary