Circadian variation of blood pressure and the vascular response to asynchronous stress

TLDR

Diurnal variation in myocardial infarction and stroke incidence may be driven by the molecular clock and/or time‑dependent environmental stress exposure. Clock gene mutations disrupt circadian blood pressure and heart rate rhythms, abolishing the 24‑hour cycle while preserving a shorter ultradian rhythm, and alter sympathoadrenal and pressor responses to stress without affecting adrenocortical activity, suggesting that the molecular clock modulates cardiovascular event timing by integrating stress responses with circadian physiology.

Abstract

The diurnal variation in the incidence of myocardial infarction and stroke may reflect an influence of the molecular clock and/or the time dependence of exposure to environmental stress. The circadian variation in blood pressure and heart rate is disrupted in mice, Bmal1(-/-), Clock(mut), and Npas2(mut), in which core clock genes are deleted or mutated. Although Bmal1 deletion abolishes the 24-h frequency in cardiovascular rhythms, a shorter ultradian rhythm remains. Sympathoadrenal function is disrupted in these mice, which reflects control of enzymes relevant to both synthesis (phenylethanolamine N-methyl transferase) and disposition (monoamine oxidase B and catechol-O-methyl transferase) of catecholamines by the clock. Both timing and disruption or mutation of clock genes modulate the magnitude of both the sympathoadrenal and pressor but not the adrenocortical response to stress. Despite diurnal variation of catecholamines and corticosteroids, they are regulated differentially by the molecular clock. Furthermore, the clock may influence the time-dependent incidence of cardiovascular events by controlling the integration of selective asynchronous stress responses with an underlying circadian rhythm in cardiovascular function.