The adrenal gland circadian clock exhibits a distinct phase advance in spontaneously hypertensive rats

Nov 23, 2018Hypertension research : official journal of the Japanese Society of Hypertension

The daily rhythm of the adrenal gland is shifted earlier in rats with high blood pressure

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Abstract

Circadian profiles of several clock genes in adrenal glands of spontaneously hypertensive rats (SHR) were phase-advanced compared to controls.

SHR displayed aberrant circadian rhythms that may influence cardiovascular parameters.
Key clock genes in the adrenal glands, including Bmal1, Per2, and Cry1, exhibited phase advancement in SHR.
Serum concentrations of corticosteroids and aldosterone were also phase advanced in SHR compared to controls.
E4bp4 gene expression was significantly higher during the dark period in SHR, but its activator, Rora, was lower throughout the 24-hour period.
Expression levels of several other clock genes tended to be lower in SHR adrenal glands than in controls.

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The circadian clock influences a multitude of cellular and biological processes, including blood pressure control. Spontaneously hypertensive rats (SHR) exhibit aberrant circadian rhythms affecting cardiovascular parameters, and they also have abnormal clock gene expression profiles in several organs. Given the important role of the adrenal gland in orchestrating circadian oscillations, we investigated the adrenal gland circadian clock in SHR and control Wistar-Kyoto rats maintained under a 12-hour light-dark cycle. Adrenal glands, livers, and serum samples were collected every 4 h and mRNA was extracted for analysis of clock gene expression. Serum levels of corticosterone and aldosterone were also analyzed. Overall, the circadian profiles of Bmal1, Per2, Per3, Cry1, RevErba, Revervb, and Dbp gene expression in SHR adrenal glands were phase-advanced relative to controls. The expression profile of StAR (a representative gene under circadian control in the adrenal gland), as well as the circadian rhythms of serum concentrations of corticosteroid and aldosterone were also phase advanced. E4bp4 gene expression was significantly higher during the dark period, yet the expression of its transcriptional activator, Rora, was significantly lower throughout the 24 h period in SHR adrenal glands than in controls. This paradoxical high E4bp4 gene expression was, however, not observed in the liver. In addition, Per1, Per2, Per3, Reverba, and Reverbb mRNA tended to be lower in SHR adrenal glands than in controls. Thus, we conclude that SHR possess an abnormal adrenal circadian clock, which may affect the transcriptional regulation of clock-controlled genes, and steroid hormone secretion by the adrenal gland.

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The adrenal gland circadian clock exhibits a distinct phase advance in spontaneously hypertensive rats

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