Circadian variation of blood pressure and the vascular response to asynchronous stress.
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.
Curtis
Anne M
AM
Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, 153 Johnson Pavilion, Philadelphia, PA 19104, USA.
Cheng
Yan
Y
Kapoor
Shiv
S
Reilly
Dermot
D
Price
Tom S
TS
Fitzgerald
Garret A
GA
D056930:ARNTL Transcription Factors; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D056926:CLOCK Proteins; D002339:Carotid Arteries / Q000601:surgery; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D008995:Monoamine Oxidase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology*; D013686:Telemetry; D015534:Trans-Activators / Q000235:genetics*
D056930:ARNTL Transcription Factors; D000305:Adrenal Cortex Hormones; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D002394:Catechol O-Methyltransferase; D002395:Catecholamines; D008995:Monoamine Oxidase; D009419:Nerve Tissue Proteins; D010625:Phenylethanolamine N-Methyltransferase; D015534:Trans-Activators; C538961:Bmal1 protein, mouse; C491259:Npas2 protein, mouse; C538944:Clock protein, mouse