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Kidney Specific Disruption of the Circadian Gene BMAL1 in Mice Produces a Sex‐ Dependent Effect on Systolic and Diastolic Blood Pressure
Author(s) -
Glasford Krystal B,
Crislip Gene Ryan,
Douma Lauren G,
Lynch Irma J,
Cheng KitYan,
Wingo Charles S,
Gumz Michelle L
Publication year - 2019
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.2019.33.1_supplement.864.14
Subject(s) - circadian rhythm , blood pressure , clock , medicine , endocrinology , period (music) , rhythm , circadian clock , diastole , kidney , knockout mouse , biology , receptor , physics , acoustics
Fluctuations in physiological functions that occur in all living organisms within a 24‐hour period are referred to as circadian rhythms. Disruptions in these rhythms are associated with cardiovascular diseases. A major goal of our lab is to find the link between circadian rhythms and cardiovascular health. Our internal clock is regulated by isoforms of four main transcriptions factors; PER, BMAL1, CLOCK and CRYPTOCHROME. Curtis et al., 2007, found that male global BMAL1 knockout mice have 10 mmHg lower blood pressure than control mice and lose their circadian rhythm. Our understanding of the regulation of circadian rhythms in blood pressure is incomplete. Thus, our objective was to investigate the effect of kidney specific BMAL1 knock out on the circadian rhythm of the diastolic blood pressure (DBP) and systolic blood pressure (SBP). Hypothesis We hypothesize that kidney‐specific BMAL1 knockout mice (KO) would lose their circadian rhythm of SBP and DBP. Methods Mouse models were generated using the Cre‐lox system. Telemeters were surgically inserted into the mice to continuously monitor blood pressure for 3 days. Blood pressure recordings were analyzed using Cosinor software to determine the MESOR, amplitude and period of the DBP and SBP data. The MESOR refers to the midline estimating statistic of rhythm which is a rhythm adjusted mean. The amplitude measures the extent of predictable change within a cycle and the period refers to the duration of a cycle, from peak to peak. WT and KO values were compared by t‐test. Results Refer to table 1 for MESOR, amplitude and period values. For SBP, male KO had significantly lower MESOR compared to WT (P=0.03). Similarly, for DBP, male KO had significantly lower MESOR compared to WT (P=0.04). For males, there were no significant differences in the amplitude or period of SBP or DBP. For females, there were no difference seen in the MESOR, amplitude or period for SBP or DBP. Conclusion Our data indicate that BMAL1 in the kidney does not contribute to circadian rhythms of blood pressure. However, BMAL1‐ dependent renal mechanisms contribute to a sex‐dependent effect on BP where only male KO experience lower mean arterial pressure compared to male WT. Support or Funding Information American Physiological Society Short‐ Term Research Education Program to Increase Diversity in Health Related Research (STRIDE); Gatorade Trust through the Department of Medicine; NIH grants R01 DK109570 (MLG), T32HL083810 (GRC) and T32DK104721 (LGD); National Heart, Lung and Blood Institute (Grant #1 R25 HL115473‐01) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .