Circadian expression of clock genes and angiotensin II type 1 receptors in suprachiasmatic nuclei of sinoaortic-denervated rats

Mar 23, 2007Acta pharmacologica Sinica

Daily patterns of internal clock genes and blood pressure receptors in the brain's main timekeeping center of rats without nerve signals from blood pressure sensors

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Abstract

Sinoaortic-denervated (SAD) rats exhibited significantly increased blood pressure variability compared to sham-operated rats.

Blood pressure levels in SAD rats were similar to those of sham-operated rats.
Circadian expression of clock genes Per2 and Bmal1 was significantly lower in SAD rats, particularly during dark periods.
The normal circadian rhythm of clock proteins was attenuated in the SCN of SAD rats.
AT1 receptor mRNA expression in the SCN was abnormally elevated during the light phase in SAD rats.
SAD rats showed a shift to a 12-hour cycle in the expression of AT1 receptors.

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AIM: To investigate whether the circadian expression of central clock genes and angiotensin II type 1 (AT1) receptors was altered in sinoaortic-denervated (SAD) rats.

METHODS: Male Sprague-Dawley rats underwent sinoaortic denervation or a sham operation at the age of 12 weeks. Four weeks after the operation, blood pressure and heart period were measured in the conscious state in a group of sham-operated (n=10) and SAD rats (n=9). Rest SAD and sham-operated rats were divided into 6 groups (n=6 in each group). The suprachiasmatic nuclei (SCN) tissues were taken every 4 h throughout the day from each group for the determination of the mRNA expression of clock genes (Per2 and Bmal1) and the AT1 receptor by RT-PCR; the protein expression of Per2 and Bmal1 was determined by Western blotting.

RESULTS: Blood pressure levels in the SAD rats were similar to those of the sham-operated rats. However, blood pressure variabilities significantly increased in the SAD rats compared with the sham-operated rats. The circadian variation of clock genes in the SCN of the sham-operated rats was characterized by a marked increase in the mRNA and protein expression during dark periods. Per2 and Bmal1 mRNA levels were significantly lower in the SAD rats, especially during dark periods. Western blot analysis confirmed an attenuation of the circadian rhythm of the 2 clock proteins in the SCN of the SAD rats. AT1 receptor mRNA expressions in the SCN were abnormally upregulated in the light phase, changed to a 12-h cycle in the SAD rats.

CONCLUSION: The circadian variation of the 2 central clock genes was attenuated in the SAD rats. Arterial baroreflex dysfunction also induced a disturbance in the expression of AT1 receptors in the SCN.

Circadian expression of clock genes and angiotensin II type 1 receptors in suprachiasmatic nuclei of sinoaortic-denervated rats

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