From the Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham (J.G.J., B.K.B., M.K., R.H.S., M.K.R., B.T., C.J., K.A.H., J.S.P., D.M.P.).
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS (J.S.S.).
Hypertension. 2020 Jun;75(6):1624-1634. doi: 10.1161/HYPERTENSIONAHA.119.13908. Epub 2020 Apr 20.
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.
人们认为钠处理和血压的昼夜节律受生物钟基因(如 Bmal1)调节。然而,关于生物钟基因对这些因素的调节知之甚少,特别是在大鼠中。我们使用一种新型的全身 Bmal1 敲除大鼠模型(),假设钠排泄的昼夜节律调节依赖于 Bmal1。使用遥测技术连续记录平均动脉压,我们观察到雄性和雌性 大鼠在 24 小时的过程中平均动脉压明显降低,与同窝对照相比。在 大鼠的两种性别中,昼夜平均动脉压模式保持完整,这与 小鼠模型形成对比。雄性 大鼠在 12 小时活动期和不活动期之间的基础钠排泄没有显著差异,表明在维持平均动脉压节律的情况下,昼夜控制不存在。然而,雌性 大鼠在活动期与不活动期相比,钠排泄明显增加,与对照组相似。因此,我们观察到昼夜血压和钠排泄控制之间存在明显的分离,这与性别有关。这些发现与女性维持钠排泄控制的能力更强一致,并且进一步证明了 Bmal1 在独立于钠排泄的昼夜血压控制中的新作用。