Abstract P003: Kidney-specific Knockout Of The Clock Protein Bmal1 Is Protective In Salt-sensitive Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2020-09, Vol.76 (Suppl_1)
• Main Authors: Crislip, Gene R, Douma, Lauren, Cheng, Kit-Yan, Roig, Emilio, Barral, Dominique, Lynch, I. Jeanette, Wingo, Charles, Gumz, Michelle L
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.76.suppl_1.P003

Abstract only Intro: Circadian clock factors, such as BMAL1, influence systemic blood pressure (BP) control. Previously, we generated renal distal segment BMAL1 knockout mice (KS-BMAL1 KO) that exhibit lower BP compared to control mice (CNTL) in males but not females. Additionally, male KS-BMAL1 KO retain less sodium following potassium depletion compared to CNTL, a difference not seen in females. Goal: The goal of this study was to test the hypothesis that male KS-BMAL1 KO display lower BP than CNTL in response to a potassium deficient, high salt diet. Methods: Our mouse model was generated using floxed exon 8 BMAL1 mice crossed with kidney-specific cadherin Cre+ mice to generate KS-BMAL1 KO. Floxed Cre- littermates were used as CNTL. Male mice were implanted with telemeter devices for 24-hour BP monitoring before and during administration of a low potassium diet over 7 days (0% K, 0.2% Na) and followed by a low potassium, high salt diet for 10 days (0% K, 2% Na, N=7-8). Two-way ANOVA was used to compare diet and genotype effects. Results: Following potassium depletion alone, systolic BP significantly decreased in both genotypes (P