Valsartan-mediated chronotherapy in spontaneously hypertensive rats via targeting clock gene expression in vascular smooth muscle cells

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.

Keywords:

• Circadian blood pressure rhythm
• valsartan chronotherapy
• clock genes
• MLC20 phosphorylation
• vascular smooth muscle cells

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the 2014 Provincial Natural Science Research Project of Anhui Higher Education Institutions (Grant No. KJ2014A262), Anhui Province Science and Technology Projects (Grant No. 1604a0802097), the 2016 Natural Science Foundation of Anhui Province (Grant No. 1608085MH178), and the China Guanghua Foundation (Grant No. KY20060212).