title: The circadian clock modulates renal sodium handling.
abstract: The circadian clock contributes to the control of BP, but the underlying mechanisms remain unclear. We analyzed circadian rhythms in kidneys of wild-type mice and mice lacking the circadian transcriptional activator clock gene. Mice deficient in clock exhibited dramatic changes in the circadian rhythm of renal sodium excretion. In parallel, these mice lost the normal circadian rhythm of plasma aldosterone levels. Analysis of renal circadian transcriptomes demonstrated changes in multiple mechanisms involved in maintaining sodium balance. Pathway analysis revealed the strongest effect on the enzymatic system involved in the formation of 20-HETE, a powerful regulator of renal sodium excretion, renal vascular tone, and BP. This correlated with a significant decrease in the renal and urinary content of 20-HETE in clock-deficient mice. In summary, this study demonstrates that the circadian clock modulates renal function and identifies the 20-HETE synthesis pathway as one of its principal renal targets. It also suggests that the circadian clock affects BP, at least in part, by exerting dynamic control over renal sodium handling.
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne, 27 rue du Bugnon, Lausanne, Switzerland.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Nikolaeva
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pradervand
authors.forename: Gabriel
authors.initials: G
authors.lastname: Centeno
authors.forename: Vlasta
authors.initials: V
authors.lastname: Zavadova
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tokonami
authors.forename: Marc
authors.initials: M
authors.lastname: Maillard
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonny
authors.forename: Dmitri
authors.initials: D
authors.lastname: Firsov
mesh_terms: D000450:Aldosterone / Q000032:analysis / Q000097:blood; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism*; D057906:Circadian Clocks / Q000235:genetics*; D004195:Disease Models, Animal; D006706:Homeostasis / Q000235:genetics; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007671:Kidney Concentrating Ability; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D012084:Renin-Angiotensin System / Q000502:physiology; D012680:Sensitivity and Specificity; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D059467:Transcriptome / Q000235:genetics
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D000450:Aldosterone; D012964:Sodium; D056926:CLOCK Proteins; C538944:Clock protein, mouse