Premium
Bmal1 knockout rats show sex differences in the rhythms of diurnal sodium excretion
Author(s) -
Johnston Jermaine G.,
Jin Chunhua,
Pollock David M.
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.lb847
Subject(s) - medicine , endocrinology , zeitgeber , circadian rhythm , excretion , clock , per1 , knockout mouse , biology , aldosterone , diurnal temperature variation , gene knockout , chemistry , circadian clock , gene , genetics , receptor , atmospheric sciences , geology
Previous studies suggest that core clock genes generally function to facilitate Na conservation such as Per1 effects to mediate the renal effects of aldosterone. Mouse models have shown that knockout of the Bmal1 gene results in multiple pathologies and a shortened life span. However, little is known about the function of Bmal1 in control of Na handling by the kidney in the rat. Therefore, we used a newly created whole‐body Bmal1KO knockout rat model (MCW Gene Editing Rat Resource Center) to determine the impact of Bmal1 gene deletion on the diurnal rhythms of sodium excretion (UNaV). Loss of Bmal1 expression was verified by Western blot. Male and female rats homozygous for the mutation (homo) and their littermate controls (wt) were implanted with telemetry transmitters to monitor mean arterial pressure (MAP). After a recovery period of at least one week, baseline urine samples were collected in 12hr light/dark intervals. The night‐day difference in UNaV was evident in wt, but not homo male rats (415 ± 87 and 14 ± 72 μEq Na/12hr wt vs. homo, n=6 and 4, respectively; P<.05). This loss of diurnal rhythm was not observed in female homo rats (274 ± 79 and 205 ± 43 μEq Na/12hr wt vs. homo, n=5 and 9, respectively; P<.05). Rats were then given a single 900μEq Na salt load (NaCl) in 1mL of water by oral gavage at the beginning of their inactive (Zeitgeber Time (ZT) 0) or active (ZT12) period. Despite the differences in night‐day UNaV between male wt and homo rats, both groups exhibited a prompt natriuretic response to an acute salt load, excreting most of the excess salt in the first 12 hours after being given either a salt load at ZT0 or ZT12. However, when comparing the total 24hr response to the salt load, the homo group displayed a higher change in UNaV compared to wt when the salt load was given at ZT0 (706 ± 78 and 1123 ± 50 μEq Na/24hr wt vs. homo, n=6 and 4, respectively; P<.05). Again, this difference was not observed in female rats. There were no significant differences in MAP between genotypes in either sex. These data suggest that rats lacking Bmal1 expression display a blunted rhythm of diurnal UNaV in male but not female rats. In addition, male Bmal1KO rats display an enhanced ability to excrete a salt challenge consistent with a sodium conserving function of clock genes by the kidney.