Male kidney-specific BMAL1 knockout mice are protected from K + -deficient, high-salt diet-induced blood pressure increases

• Published in: American journal of physiology. Renal physiology Vol. 325; no. 5; p. F656
• Main Authors: Crislip, G Ryan, Costello, Hannah M, Juffre, Alexandria, Cheng, Kit-Yan, Lynch, I Jeanette, Johnston, Jermaine G, Drucker, Charles B, Bratanatawira, Phillip, Agarwal, Annanya, Mendez, Victor M, Thelwell, Ryanne S, Douma, Lauren G, Wingo, Charles S, Alli, Abdel A, Scindia, Yogesh M, Gumz, Michelle L
• Format: Journal Article
• Language: English
• Published: United States 01-11-2023
• Subjects: Animals; ARNTL Transcription Factors - metabolism; Blood Pressure - physiology; Circadian Rhythm - physiology; Cytokines; Diet; Hypertension - genetics; Hypertension - prevention & control; Kidney - metabolism; Male; Mice; Mice, Knockout; Sodium Chloride, Dietary; immune cells; clock; inflammation; hypertension; circadian rhythm
• ISSN: 1522-1466
• DOI: 10.1152/ajprenal.00126.2023

The circadian clock protein basic helix-loop-helix aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a transcription factor that impacts kidney function, including blood pressure (BP) control. Previously, we have shown that male, but not female, kidney-specific cadherin Cre-positive BMAL1 knockout (KS-BMAL1 KO) mice exhibit lower BP compared with littermate controls. The goal of this study was to determine the BP phenotype and immune response in male KS-BMAL1 KO mice in response to a low-K
high-salt (LKHS) diet. BP, renal inflammatory markers, and immune cells were measured in male mice following an LKHS diet. Male KS-BMAL1 KO mice had lower BP following the LKHS diet compared with control mice, yet their circadian rhythm in pressure remained unchanged. Additionally, KS-BMAL1 KO mice exhibited lower levels of renal proinflammatory cytokines and immune cells following the LKHS diet compared with control mice. KS-BMAL1 KO mice were protected from the salt-sensitive hypertension observed in control mice and displayed an attenuated immune response following the LKHS diet. These data suggest that BMAL1 plays a role in driving the BP increase and proinflammatory environment that occurs in response to an LKHS diet.
We show here, for the first time, that kidney-specific BMAL1 knockout mice are protected from blood pressure (BP) increases and immune responses to a salt-sensitive diet. Other kidney-specific BMAL1 knockout models exhibit lower BP phenotypes under basal conditions. A salt-sensitive diet exacerbates this genotype-specific BP response, leading to fewer proinflammatory cytokines and immune cells in knockout mice. These data demonstrate the importance of distal segment BMAL1 in BP and immune responses to a salt-sensitive environment.