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


CONCLUSIONS
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.
Li
Hui
H
Department of Cardiology, Peking University People's Hospital, Beijing 100044, China.
Sun
Ning-ling
NL
Wang
Jin
J
Liu
Ai-jun
AJ
Su
Ding-feng
DF
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D003714:Denervation; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D056950:Period Circadian Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics*; D012849:Sinoatrial Node / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics*
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D044140:Receptor, Angiotensin, Type 1; D015534:Trans-Activators; C513311:Per2 protein, rat; C538945:Clock protein, rat