Effect of upregulated renin-angiotensin system on per2 and bmal1 gene expression in brain structures involved in blood pressure control in TGR(mREN-2)27 rats.

Circadian system regulates rhythms with 24 h period including those occurring in the cardiovascular system. Inverted blood pressure profile was demonstrated in hypertensive TGR(mREN-2)27 (TGR) rats with upregulated renin-angiotensin system. To depict structures involved in the generation of the inverted pattern of blood pressure in TGR rats, we analyzed daily expression of clock genes per2 and bmal1 in the brain areas involved in the regulation of the blood pressure. Heterozygous male TGR and control rats were synchronized to the light:dark cycle 12:12 and blood samples were taken in 4 h intervals within 24 h cycle. The levels of the plasma renin activity were increased in TGR rats in comparison with controls. Brain nuclei were isolated by dissection from frozen sections. The clock gene expression was determined in the hypothalamic paraventricular and dorsomedial nuclei, dorsal vagal motor nucleus, caudal ventrolateral medulla, nucleus ambiguus, area postrema, and anteroventral third ventricle. Daily pattern of per2 expression was rhythmic in most of the nuclei studied with its highest levels at the beginning of the nighttime in both groups of rats. Expression of bmal1 peaked at the beginning of the day. We found robust differences in the clock gene expression between the TGR and control rats in the area postrema. TGR rats exerted changes in the clock gene expression in the nucleus ambiguus which receives direct innervation from the area postrema. The area postrema seems to play a key role in the transmission of signals from the periphery to the CNS.