Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 318, Issue 6, Pages F1463-F1477Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00014.2020
Keywords
blood pressure; brain and muscle ARNT-like 1; clock genes; gene expression; potassium depletion; sex differences
Categories
Funding
- NHLBI NIH HHS [T32 HL083810] Funding Source: Medline
- NIDDK NIH HHS [F32 DK121424, T32 DK104721] Funding Source: Medline
- NIH HHS [5T32DK104721, 5T32HL083810-10, 1R01DK109570-01A1] Funding Source: Medline
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The renal circadian clock has a major influence on the function of the kidney. Aryl hydrocarbon receptor nuclear translocator-like protein 1 [ARNTL; also known as brain and muscle ARNT-like 1 (BMAL1)] is a core clock protein and transcription factor that regulates the expression of nearly half of all genes. Using male and female kidney-specific cadherin BMAL1 knockout (KS-BMAL1 KO) mice, we examined the role of renal distal segment BMALI in blood pressure control and solute handling. We confirmed that this mouse model does not express BMAL1 in thick ascending limb, distal convoluted tubule, and collecting duct cells. which are the final locations for solute and fluid regulation. Male KS-BMAL1 KO mice displayed a substantially lower basal systolic blood pressure compared with littermate control mice, yet their circadian rhythm in pressure remained unchanged [male control mice: 127 +/- 0.7 mmHg (n = 4) vs. male KS-BMAL KO mice: 119 +/- 2.3 mmHg (n = 5), P < 0.05]. Female mice. however, did not display a genotype difference in basal systolic blood pressure [female control mice: 120 +/- 1.6 mmHg (n = 5) vs. female KS-BMAL1 KO mice: 119 +/- 1.5 mmHg (n = 7), P = 0.4]. In addition, male KS-BMAL1 KO mice had less Na+ retention compared with control mice in response to a K+-restricted diet (15% less following 5 days of treatment). However, there was no genotype difference in Na+ handling after a K+-restricted diet in female mice. Furthermore, there was evidence indicating a sex-specific response to K restriction where female mice reabsorbed less Na+ in response to this dietary challenge compared with male mice. We propose that BMAL1 in the distal nephron and collecting duct contributes to blood pressure regulation and Na+ handling in a sex-specific manner.
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