2021
DOI: 10.1093/ajh/hpab047
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Chronic Blockade of NMDAR Subunit 2A in the Hypothalamic Paraventricular Nucleus Alleviates Hypertension Through Suppression of MEK/ERK/CREB Pathway

Abstract: Background N-methyl-D-aspartate Receptor (NMDAR) in the hypothalamic paraventricular nucleus (PVN) plays critical roles in regulating sympathetic outflow. Studies showed that acute application of the antagonists of NMDAR or its subunits would reduce sympathetic nerve discharges. However, little is known about the effect of long-term management of NMDAR in hypertensive animals. Methods PEAQX, the specific antagonist of NMDAR s… Show more

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Cited by 9 publications
(7 citation statements)
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“…NMDAR is also related to encephalitis and myocardial infarction ( Danysz and Parsons, 2003 ; Olivares et al, 2012 ; Wang et al, 2015 ; Jannesar et al, 2020 ). Our recent study demonstrated that the expression level of NMDAR subunits is elevated during hypertension, and chronic blockade of NMDAR subunit 2A (GluN2A) in the PVN alleviates hypertension ( Li et al, 2021 ). Studies have found that Nrf1 is functionally related to the promoters of GluN1 and GluN2B.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…NMDAR is also related to encephalitis and myocardial infarction ( Danysz and Parsons, 2003 ; Olivares et al, 2012 ; Wang et al, 2015 ; Jannesar et al, 2020 ). Our recent study demonstrated that the expression level of NMDAR subunits is elevated during hypertension, and chronic blockade of NMDAR subunit 2A (GluN2A) in the PVN alleviates hypertension ( Li et al, 2021 ). Studies have found that Nrf1 is functionally related to the promoters of GluN1 and GluN2B.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, research found that regions with high oxidative stress have higher levels of glutamatergic and NMDAR-mediated synapses, and that the level of ROS and NMDAR subunits reduces simultaneously when excitatory transmission is suppressed ( Wong-Riley M. et al, 1998 ; Wong-Riley M. T. et al, 1998 ). During hypertension, both level of ROS and expression of NMDAR increase ( Li et al, 2021 ). It is likely that Nrf1 regulates ROS and NMDAR at the same time.…”
Section: Introductionmentioning
confidence: 99%
“…The NOX4, interleukin 6 (IL-6) and interleukin 1β (IL-1β) gene expression were quantified through real-time PCR assays. The specific operation process is the same as previously described [ 32 , 33 ] and the following primer sequences were used (See Table 1 ).…”
Section: Methodsmentioning
confidence: 99%
“…It also affects the expression of cascade mitogen-activated protein kinase (MAPK), cAMP response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF). NMDAR also affects the normal expression of proteins related to learning and memory such as PSD-95, NR2A, NR2B, and phosphatidylinositol 3 kinase (PI3K) (60). PSD-95 is a key skeleton protein of NMDAR and neuronal nitric oxide synthase (nNOS), which plays an important role in neural development (61).…”
Section: Nmdarmentioning
confidence: 99%