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P2X7 receptor regulates sympathoexcitatory response in myocardial infarction rats via NF-?B and MAPK pathways.


ABSTRACT: Previous studies have provided evidence for the regulatory effect of P2X7 receptor (P2X7R) on cardiovascular activities. Our study focused on exploring the function and fundamental mechanism of microglial P2X7R in controlling sympathoexcitatory response using rats with acute myocardial infarction (AMI). Coronary artery ligation was used in rats to cause AMI. And before that, rats were administrated with P2X7R siRNA that targeted P2X7R mRNA into paraventricular nucleus (PVN) or BBG (Brilliant Blue G, a P2X7 receptor antagonist). Increased expression levels of P2X7R and adenosine triphosphate (ATP) were observed in the hypothalamic PVN of AMI rats. Moreover, the knockdown of P2X7R expression by P2X7-siRNA or suppression of P2X7 receptor by BBG attenuated the elevation of both vasopressin and oxytocin levels in the PVNs of AMI rats. There was also a decrease in renal sympathetic nerve activity (RSNA) by P2X7-siRNA and BBG. Besides, inflammation was alleviated by P2X7-siRNA and BBG through suppressing pro-inflammatory cytokines IL-1? and IL-6 in PVN of AMI rats. Furthermore, blockade of P2X7R moderated the process of cardiac remodeling. This was achieved due to the regulatory effect of P2X7R on sympathoexcitatory response by influencing NF-?B and mitogen-activated protein kinase (MAPK) signaling. These findings suggest that P2X7R can act as a new regulator of sympathoexcitatory response via NF-?B and MAPK signaling pathways in AMI rats.

SUBMITTER: Wu Q 

PROVIDER: S-EPMC5714779 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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P2X7 receptor regulates sympathoexcitatory response in myocardial infarction rats via NF-κB and MAPK pathways.

Wu Qin Q   Xu Hongtao H   Hao Ling L   Ma Guifang G   Sun Jinxia J   Song Xianghe X   Ding Fengyun F   Wang Nan N  

American journal of translational research 20171115 11


Previous studies have provided evidence for the regulatory effect of P2X7 receptor (P2X7R) on cardiovascular activities. Our study focused on exploring the function and fundamental mechanism of microglial P2X7R in controlling sympathoexcitatory response using rats with acute myocardial infarction (AMI). Coronary artery ligation was used in rats to cause AMI. And before that, rats were administrated with P2X7R siRNA that targeted P2X7R mRNA into paraventricular nucleus (PVN) or BBG (Brilliant Blu  ...[more]

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