[Animal experiment]-Hypothalamic paraventricular nucleus NMDAR mediates the role of rat pro-inflammatory factors to enhance the sympathetic activity of hypertension

  Objective: Whether the inflammatory cytokines in the paraventricular nucleus of the hypothalamus in spontaneously hypertensive rats (SHR) promote sympathetic hyperactivity and whether they are N-methyl-D-aspartate receptors (N-methyl). Research-D-aspartate receptors (NMDARs) mediate the above effects.

  Method: This study uses adult SHR and Wistar-Kyoto (WKY) rats with normal blood pressure. Western-blot analysis and enzyme-linked immunosorbent assay (ELISA) were used to detect paraventricular nucleus (PVN) tumor necrosis factor (TNF) and interleukin (IL)-1β receptor IL-, respectively. Determine the expression of 1I protein and the levels of TNF-α and IL-1β. And use stereotactic technology for PVN micro-drug injection. Use Powerlab system to measure renal sympathetic nerve activity (RSNA), record renal sympathetic nerve trunk electrical activity, and perform comprehensive treatment to compare the changes of RSNA before and after administration. The carotid artery cannula is connected to the PowerLab system through a pressure sensor to record and analyze mean arterial pressure (MAP).

  Results: Compared with WKY rats, the levels of TNF-α and IL-1β in SHRPVN and the protein expression of TNF-α receptor p55TNFR, p75TNFR and IL-1β receptor IL-1RI increased significantly (P\u003c0.05 ). PVN microinjection of etanercept or IL-1ra can block the effects of TNF-α and IL-1β, and significantly reduce the activity of sympathetic nerves in the SHR group (P\u003c0.05). PVN microinjection of NMDAR antagonist DL-2-amino-5-phosphonate glutarate (APV) or MK-801 (biszocepine) can reduce RSNA and MAP in SHR and WKY groups (P\u003c0.05) , The effect of SHR group is greater. Significant (P\u003c0.05); in addition, pretreatment with APV or MK-801 to block the NMDA receptor of PVN can significantly reduce the effect of PVN microinjection of TNF-α or IL-1β, and increase RSNA. The MAP of SHR and WKY groups was enhanced and increased. (P\u003c0.05) Compared with the SHR group, the effect of the SHR group was more obvious (P\u003c0.05).

  Conclusion: SHRPVN pro-inflammatory cytokines TNF-α, IL-1β and their receptors all increase. PVNMDA receptor mediates TNF-α and IL-1β in PVN of SHR rats to promote sympathetic nerve activity and blood pressure. Nurturing effect.