The diurnal rhythms of sodium handling and blood pressure are thought to be regulated by clock genes, such as Bmal1. However, little is known about the regulation of these factors by Bmal1, especially in rats. Using a novel whole-body Bmal1 knockout rat model (), we hypothesized that time of day regulation of sodium excretion is dependent on Bmal1. Using telemetry to continuously record mean arterial pressure, we observed that male and female rats had significantly reduced mean arterial pressure over the course of 24 hours compared with littermate controls. The circadian mean arterial pressure pattern remained intact in both sexes of rats, which is in contrast to the mouse model. Male rats had no significant difference in baseline sodium excretion between 12-hour active and inactive periods, indicating a lack of diurnal control independent of maintained mean arterial pressure rhythms. Female rats, however, had significantly greater sodium excretion during the active versus inactive period similar to controls. Thus, we observed a clear dissociation between circadian blood pressure and control of sodium excretion that is sex dependent. These findings are consistent with a more robust ability of females to maintain control of sodium excretion, and furthermore, demonstrate a novel role for Bmal1 in control of diurnal blood pressure independent of sodium excretion.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13908 | DOI Listing |
J Clin Med
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The Second Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan.
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Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
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Translational Research On Renal and Cardiovascular Diseases (TRECARD), Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain. Electronic address:
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Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
Several sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to have beneficial effects on renal function in patients with type 2 diabetes. However, the long-term effects of luseogliflozin, an SGLT2 inhibitor, remain uncertain in real-world settings. This multicenter, open-label, prospective observational study evaluated the long-term effects of luseogliflozin on renal function in Japanese patients with type 2 diabetes.
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School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P.R. China.
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