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Publication : The circadian clock modulates renal sodium handling.

First Author  Nikolaeva S Year  2012
Journal  J Am Soc Nephrol Volume  23
Issue  6 Pages  1019-26
PubMed ID  22440902 Mgi Jnum  J:264294
Mgi Id  MGI:6195090 Doi  10.1681/ASN.2011080842
Citation  Nikolaeva S, et al. (2012) The circadian clock modulates renal sodium handling. J Am Soc Nephrol 23(6):1019-26
abstractText  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.
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