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

Area of Science:

• Chronobiology
• Cardiovascular Physiology
• Molecular Biology

Background:

• Diurnal variations in myocardial infarction and stroke suggest a role for the molecular clock and environmental stress timing.
• Circadian rhythms in blood pressure and heart rate are known to be disrupted in mice with mutations in core clock genes (Bmal1, Clock, Npas2).

Purpose of the Study:

• To investigate the influence of the molecular clock on cardiovascular rhythms and stress responses.
• To understand how clock gene disruption affects sympathoadrenal function and catecholamine metabolism.
• To elucidate the clock's role in the time-dependent incidence of cardiovascular events.

Main Methods:

• Analysis of cardiovascular rhythms in mice with deleted or mutated core clock genes (Bmal1(-/-), Clock(mut), Npas2(mut)).
• Assessment of sympathoadrenal function, including enzyme activity related to catecholamine synthesis and disposition.
• Evaluation of pressor and adrenocortical responses to stress in relation to clock gene status and timing.

Main Results:

• Bmal1 deletion abolished 24-hour cardiovascular rhythms but a shorter ultradian rhythm persisted.
• Sympathoadrenal function was disrupted in mutant mice, affecting enzymes like phenylethanolamine N-methyl transferase, monoamine oxidase B, and catechol-O-methyl transferase.
• Clock gene disruption modulated sympathoadrenal and pressor responses to stress, but not adrenocortical responses.

Conclusions:

• The molecular clock differentially regulates catecholamines and corticosteroids, influencing cardiovascular function.
• Clock genes play a critical role in integrating stress responses with underlying circadian cardiovascular rhythms.
• The molecular clock may mediate the time-dependent incidence of cardiovascular events through coordinated stress response and cardiovascular rhythm regulation.