The Central Deacetylase Sirtuin1 Decreases Sympathetic Hyperactivity by Anti‐oxidative Stress in Hypertensive Rats

Abstract

Hypertension is characterized by sympathetic hyperactivity, which is associated with pathophysiological progressing of hypertension. The rostral ventral lateral medulla (RVLM) plays a vital role of the sympathetic activity and blood pressure regulation. The NAD‐dependent deacetylase Sirtuin1 (Sirt1) plays an organ protective role by regulating the transcription of its target genes. Sirt1 is reported to show a protective effect in circulation system such as heart and blood vessel. However, it is not clear if Sirt1 in the RVLM is involved in modulating the central control of cardiovascular activity in hypertension. In our research work, Sirt1 was detected to be expressed in the catecholaminergic neurons in the RVLM, and Sirt1 was downregulated in the RVLM of the spontaneous hypertensive rats (SHR) compared with normotensive WKY rats. Chronic central administration of resveratrol (a specific agonist of Sirt1, 4 weeks) or injection of lentivirus containing Sirt1 gene in the RVLM produced a significant decrease in blood pressure, heart rate and renal sympathetic nerve activity in SHR but not in WKY rats. Furthermore, high level of reactive oxygen species in the RVLM was significantly reduced in SHR treated with over‐expression of Sirt1 gene in the RVLM. In summary, the present data suggest that Sirt1 in the RVLM exerts an anti‐hypertensive effect, which is associated with anti‐oxidative stress.Support or Funding InformationThis work was supported by NSCF (81570385 and 31500933)