Local Renal Circadian Clocks Control Fluid-Electrolyte Homeostasis and BP.

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.

PID Serval

serval:BIB_98248DEAD541

DOI

10.1681/ASN.2013060641

PMID

24652800

WOS

000338176500010

Permalien

https://iris.unil.ch/handle/iris/214952

Date de création

2014-08-05T16:42:12.198Z

Date de création dans IRIS

2025-05-21T03:50:03Z

Fichier(s)

Nom

BIB_98248DEAD541.P001.pdf

Version du manuscrit

postprint

Taille

9.31 MB

Format

Adobe PDF

PID Serval

serval:BIB_98248DEAD541.P001

URN

urn:nbn:ch:serval-BIB_98248DEAD5414

Somme de contrôle

(MD5):74354d1a3f856cedbee1ec076f7c9a1c