Peripheral circadian clock rhythmicity is retained in the absence of adrenergic signaling.
OBJECTIVE
The incidence of heart attack and stroke undergo diurnal variation. Molecular clocks have been described in the heart and the vasculature; however it is largely unknown how the suprachiasmatic nucleus (SCN) entrains these peripheral oscillators.


RESULTS
Norepinephrine and epinephrine, added to aortic smooth muscle cells (ASMCs) in vitro, altered Per1, E4bp4, and dbp expression and altered the observed oscillations in clock gene expression. However, oscillations of Per1, E4bp4, dbp, and Per2 were preserved ex vivo in the aorta, heart, and liver harvested from dopamine beta-hydroxylase knockout mice (Dbh-/-) that cannot synthesize either norepinephrine or epinephrine. Furthermore, clock gene oscillations in heart, liver, and white adipose tissue phase shifted identically in Dbh-/- mice and in Dbh+/- controls in response to daytime restriction of feeding. Oscillation of clock genes was similarly preserved ex vivo in tissues from Dbh+/- and Dbh-/- chronically treated with both propranolol and terazosin, thus excluding compensation by dopamine in Dbh-/- mice.


CONCLUSIONS
Although adrenergic signaling can influence circadian timing in vitro, peripheral circadian rhythmicity is retained despite its ablation in vivo.
Reilly
Dermot F
DF
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA.
Curtis
Anne M
AM
Cheng
Yan
Y
Westgate
Elizabeth J
EJ
Rudic
Radu D
RD
Paschos
Georgios
G
Morris
Jacqueline
J
Ouyang
Ming
M
Thomas
Steven A
SA
FitzGerald
Garret A
GA
D000818:Animals; D001011:Aorta / Q000166:cytology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D004837:Epinephrine / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D018797:Cell Cycle Proteins; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine; D004837:Epinephrine