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Publication : Importance of the renal ion channel TRPM6 in the circadian secretion of renin to raise blood pressure.

First Author  Funato Y Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  3683
PubMed ID  34140503 Mgi Jnum  J:308363
Mgi Id  MGI:6725481 Doi  10.1038/s41467-021-24063-2
Citation  Funato Y, et al. (2021) Importance of the renal ion channel TRPM6 in the circadian secretion of renin to raise blood pressure. Nat Commun 12(1):3683
abstractText  Blood pressure has a daily pattern, with higher values in the active period. Its elevation at the onset of the active period substantially increases the risk of fatal cardiovascular events. Renin secretion stimulated by renal sympathetic neurons is considered essential to this process; however, its regulatory mechanism remains largely unknown. Here, we show the importance of transient receptor potential melastatin-related 6 (TRPM6), a Mg(2+)-permeable cation channel, in augmenting renin secretion in the active period. TRPM6 expression is significantly reduced in the distal convoluted tubule of hypotensive Cnnm2-deficient mice. We generate kidney-specific Trpm6-deficient mice and observe a decrease in blood pressure and a disappearance of its circadian variation. Consistently, renin secretion is not augmented in the active period. Furthermore, renin secretion after pharmacological activation of beta-adrenoreceptor, the target of neuronal stimulation, is abrogated, and the receptor expression is decreased in renin-secreting cells. These results indicate crucial roles of TRPM6 in the circadian regulation of blood pressure.
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