title: Local renal circadian clocks control fluid-electrolyte homeostasis and BP.
abstract: The circadian timing system is critically involved in the maintenance of fluid and electrolyte balance and BP control. However, the role of peripheral circadian clocks in these homeostatic mechanisms remains unknown. We addressed this question in a mouse model carrying a conditional allele of the circadian clock gene Bmal1 and expressing Cre recombinase under the endogenous Renin promoter (Bmal1(lox/lox)/Ren1(d)Cre mice). Analysis of Bmal1(lox/lox)/Ren1(d)Cre mice showed that the floxed Bmal1 allele was excised in the kidney. In the kidney, BMAL1 protein expression was absent in the renin-secreting granular cells of the juxtaglomerular apparatus and the collecting duct. A partial reduction of BMAL1 expression was observed in the medullary thick ascending limb. Functional analyses showed that Bmal1(lox/lox)/Ren1(d)Cre mice exhibited multiple abnormalities, including increased urine volume, changes in the circadian rhythm of urinary sodium excretion, increased GFR, and significantly reduced plasma aldosterone levels. These changes were accompanied by a reduction in BP. These results show that local renal circadian clocks control body fluid and BP homeostasis.
authors.affiliation: Department of Pharmacology and Toxicology and.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tokonami
authors.affiliation: Department of Pharmacology and Toxicology and.
authors.forename: David
authors.initials: D
authors.lastname: Mordasini
authors.affiliation: Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland;
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pradervand
authors.affiliation: Department of Pharmacology and Toxicology and.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Centeno
authors.affiliation: Department of Pharmacology and Toxicology and Nestlé Institute of Health Sciences, Lausanne, Switzerland;
authors.forename: Céline
authors.initials: C
authors.lastname: Jouffe
authors.affiliation: Service of Nephrology, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and.
authors.forename: Marc
authors.initials: M
authors.lastname: Maillard
authors.affiliation: Department of Pharmacology and Toxicology and Service of Nephrology, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonny
authors.affiliation: Department of Pharmacology and Toxicology and Nestlé Institute of Health Sciences, Lausanne, Switzerland;
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gachon
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: R Ariel
authors.initials: RA
authors.lastname: Gomez
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: Maria Luisa S
authors.initials: ML
authors.lastname: Sequeira-Lopez
authors.affiliation: Department of Pharmacology and Toxicology and dmitri.firsov@unil.ch.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Firsov
mesh_terms: D056930:ARNTL Transcription Factors / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D057906:Circadian Clocks / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D012083:Renin / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D012083:Renin