Premium
Loss of Bmal1 impairs the diurnal rhythm in sodium excretion that parallels the loss of circadian blood pressure rhythm
Author(s) -
Zhang Dingguo,
Najarro Guillermo,
Chen Daian,
Obi Ijeoma,
Jin Chunhua,
Speed Joshua,
Pollock Jennifer,
Pollock David
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.855.13
Subject(s) - excretion , circadian rhythm , medicine , endocrinology , chemistry , blood pressure , sodium , urine , organic chemistry
High salt intake correlates with elevated levels of blood pressure, leading to an increased risk of cardiovascular disease. Abnormal diurnal rhythm in sodium excretion is often found in patients that exhibit non‐dipping of blood pressure. Our recent findings suggest that high salt diet alters clock gene expression patterns. The current study was designed to test the hypothesis that the circadian gene Bmal1 regulates diurnal electrolyte excretion and blood pressure in response to different levels of dietary salt. We utilized Bmal1 knockout ( Bmal1KO) (n=6) and wildtype (WT) mice in metabolic cages under normal (0.4%) and high salt (4%) diets and collected urine during active (lights‐off) and inactive (lights‐on) phases. We found that urinary sodium excretion in WT mice was higher during the active phase and lower during the inactive phase in response to normal or high salt diet (normal salt: 41±4μEq/12h vs. 21±5μEq/12h; high salt: 490±50μEq/12h vs. 100±20μEq/12h). Interestingly, in Bmal1KO mice the difference in sodium excretion was not significant between active and inactive phases (normal salt: 20±5μEq/12h vs. 11±4μEq/12h; high salt: 173±35μEq/12h vs. 101±19μEq/12h), indicating loss of diurnal Na + excretion patterns. Similarly, we found that in WT mice, urinary potassium excretion was higher in the active phase and lower in the inactive phase (normal salt: 85±10μEq/12h vs. 29±12μEq/12h; high salt: 146±9μEq/12h vs. 74±8μEq/12h); however, Bmal1KO mice showed a similar potassium excretion pattern in active and inactive phases under normal salt diet, and an even higher urinary potassium in the inactive phase when challenged with high salt (23±4μEq/12h vs. 38±6μEq/12h). Finally, Bmal1KO mice exhibited a loss of diurnal blood pressure (measured by telemetry) rhythm on both diets. These data suggest that Bmal1 is important for maintaining the diurnal pattern in sodium excretion that mirrors the loss of circadian blood pressure rhythm.