Valsartan-mediated chronotherapy in spontaneously hypertensive rats via targeting clock gene expression in vascular smooth muscle cells. (4th March 2022)

• Record Type: Journal Article
• Authors: Luan, Jiajie; Yang, Kui; Ding, Yanyun; Zhang, Xiaotong; Wang, Yaqin; Cui, Haiju; Zhou, Deixi; Chen, Lu; Ma, Zhangqing; Wang, Wusan; Zhang, Wen; Liu, Xiaoyun
• Is Part Of: Archives of physiology and biochemistry. Volume 128:Number 2(2022)
• Page Start: 490
• Page End: 500
• Publication Date: 2022-03-04
• Subjects: Circadian blood pressure rhythm -- valsartan chronotherapy -- clock genes -- MLC20 phosphorylation -- vascular smooth muscle cells; Physiology -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Biochemistry; Physiology; 571
• DOI: 10.1080/13813455.2019.1695840
• Languages: English
• ISSNs: 1381-3455

Abstract

Abstract: Objective: This study was to investigate the underlying mechanisms of valsartan chronotherapy in regulating blood pressure variability. Methods: RT-PCR was used to assay clock genes expression rhythm in the hypothalamus, aortic vessels, and target organs after valsartan chronotherapy. WB was used to measure Period 1 (Per1), Period 2 (Per2) protein expression in aortic vessels, as well as to measure phosphorylation of 20-kDa regulatory myosin light chain (MLC20 ) in VSMCs. Results: Specific clock genes in the hypothalamus, and Per1 and Per2 in aorta abdominalis, exhibited disordered circadian expression in vivo . Valsartan asleep time administration (VSA) restored circadian clock gene expression in a tissue- and gene-specific manner. In vitro, VSA was more efficient in blocking angiotensin II relative to VWA, which led to differential circadian rhythms of Per1 and Per2, ultimately corrected MLC20 phosphorylation. Conclusion: VSA may be efficacious in regulating circadian clock genes rhythm, then concomitantly correct circadian blood pressure rhythms.