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The Circadian Clock Modulates Renal Sodium Handling

2012; American Society of Nephrology; Volume: 23; Issue: 6 Linguagem: Inglês

10.1681/asn.2011080842

1533-3450

Svetlana Nikolaeva, Sylvain Pradervand, Gabriel Centeno, Vlasta Zavadova, Natsuko Tokonami, Marc Maillard, Olivier Bonny, Dmitri Firsov,

Ion Transport and Channel Regulation

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.