e0086 Sinoaortic denervation disrupted the circadian rhythm of the oscillation of molecular clock and activity of RAS in cardiovascular

Objective To observe the profile of blood pressure in sinoaortic denervated (SAD) rats and investigate the expression of clock genes per2, BMAL1, clock output gene DBP, AT1 and PCNA in heart and thoracic aortic of SD and SAD rats, therefore to probe into the influences of the impairment of arterial baroreflex (ABR) on molecular clock and the activity of RAS in peripheral cardiovascular and their interaction. Methods 72 male Sprague-Dawley rats underwent SAD or sham operation at the age of 12 weeks. 24-h BP and BPV were measured in conscious and unrestrained rats 4 weeks after operation. Rats were housed in a 12 h light/12 h dark cycle (LD12:12) for at least 10 days. Heart and thoracic aorta were taken every 4 h throughout the day to investigate mRNA expression of clock genes (per2, BMAL1), clock output gene DBP, AT1 receptors and PCNA by RT-real time PCR and examine the abundance of Per2 protein in heart and vessel tissue by Western Blotting respectively. Results Compared with sham-operated rats, SBPV and DBPV over 24 h of SAD rats were enlarged (p<0.01). Clock genes (Per2 and BMAL1), clock output gene DBP, AT1 receptors and PCNA oscillated synchronously both in heart and vascular of SAD and sham-operated rats under light-dark cycle. After sinoaortic denervation, the total mRNA abundance of Per2 decreased significantly both in heart and aorta (p<0.05 or p<0.01). BMAL1, DBP, AT1 and PCNA in heart were up-regulated significantly (p<0.05 or p<0.01), while that of these genes in aortic remained unchanged. More importantly, after operation, the circadian rhythm of mRNA expression of all the above genes both in heart and aortic changed significantly, showing an abnormal expression level of these genes by a rough normal diurnal and nocturnal pattern in heart, or by diurnal oscillation patterns in aorta. Consistent with Per2 mRNA expression, its protein abundance in heart and aortic decreased simultaneously, and the circadian rhythm was also disturbed. Moreover, all the amplitude of the mentioned genes were significantly weakened or enlarged in SAD rats. Conclusions The impairment of arterial baroreflex leads to the abnormality in the circadian rhythm of the molecular clocks and the RAS activity was mediated by AT1 in peripheral cardiovascular. The abnormality of the total RAS activity, circadian rhythm of RAS activity in peripheral tissues, disorders of molecular clock as well as the abnormality of RAS activity may all contribute to the upset of molecular clock in peripheral cardiovascular following sinoaortic denervation. Therefore these abnormalities promote dysfunction of BP regulation and proliferation and remodelling of cardiovascular in SAD rats.