scholarly journals Angiotensin II (AngII) “slow‐pressor” hypertension enhances p47 membrane translocation and glutamate receptor‐induced production of reactive oxygen species (ROS) in hypothalamic paraventricular nucleus (PVN) neurons

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Gang Wang ◽  
Christal G Coleman ◽  
Xian Cao ◽  
Joan Zhou ◽  
Robin L Davisson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Glutamate Receptor ◽  
Paraventricular Nucleus ◽  
Reactive Oxygen ◽  
Hypothalamic Paraventricular Nucleus ◽  
Oxygen Species ◽  
Membrane Translocation

Abstract 032: Microglial TLR4 Mediate Angiotensin II-induced Reactive Oxygen Species Production within the Paraventricular Nucleus in Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Vinicia C Biancardi ◽  
Javier E Stern
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Paraventricular Nucleus ◽  
Reactive Oxygen ◽  
Microglia Activation ◽  
Molecular Evidence ◽  
Ros Production ◽  
Oxygen Species ◽  
Indirect Measure

Angiotensin II (AngII) contribution to hypertension involves CNS inflammation that includes cytokine release and reactive oxygen species (ROS) production. The innate immune system, via TLR4 signaling, has been implicated in AngII-mediated inflammatory responses. Yet, whether microglia, the immune cells of the CNS, are key cell targets mediating these effects is still unknown. Thus, we studied here whether TLR4 is a molecular link connecting AngII mediated microglia activation and ROS production within the paraventricular nucleus (PVN) during hypertension. TLR4 and AngII type 1 receptor (AT1) mRNA expression was found in isolated PVN microglia, providing molecular evidence for AT1/TLR4 crosstalk. Isolated microglia TLR4 mRNA expression was 2.56*-fold higher in hypertension. TLR4 and microglia (IBA1) immunoreactivity density were increased in the PVN of SHR vs WKY (TLR4 1.8±0.02 vs 1.3±0.1*; IBA1 23±3.03 vs 13.6±0.6* Arbitrary units - AU). Altered density was attenuated in SHR treated with AT1 blocker Losartan (1.3±0.05 and 14.9±0.9 AU). Higher TLR4/IBA1 co-localization was found in SHR vs WKY (4.6±0.9 vs 1.3±0.2* AU), supporting microglia activation and TLR4 upregulation in hypertension. To study whether AngII-induced microglia activation and ROS production involved TLR4, we used TLR4 deficient (TLR4-D, C3H/HeJ) and sufficient (TLR4-S, C3H/OuJ) mice. Acute hypothalamic slices exposed to AngII (1μM, 60 min) showed increased IBA1 density in the PVN of TLR4-S (3.9±0.1 to 6.5±0.3*%) and WKY (9.8±1.1 to 16.2±1.4*%). This effect was blunted in TLR4-D (4.3±0.1 to 5.2±0.5%). In SHR, AngII failed to further promote microglia activation (17.3±1.8 vs 14.1±1.1 AU). AngII (1 μΜ) increased dihydroethidium (DHE) staining (an indirect measure of ROS) in the PVN of WKY (166±2*) and TLR4-S (129±2*) compared to vehicle (100±3%). This effect was blunted in TLR4-D (102±2%). AngII-induced ROS production was attenuated by the microglia inhibitor minocycline (100 μΜ, 131±2*%) and blunted by Losartan (2 μΜ, 111±6%), suggesting AngII-ROS production involves microglia and AT1. Our results support a major contribution of microglial TLR4 to AngII-mediated ROS and microglia activation within the PVN, actions that are upregulated in hypertension. *P<0.05.

scholarly journals Role of NAD(P)H Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Cardioprotection of Ischemic Reperfusion Injury by Angiotensin II

Hypertension ◽  
2005 ◽  
Vol 45 (5) ◽  
pp. 860-866 ◽  
Author(s):  
Shoji Kimura ◽  
Guo-Xing Zhang ◽  
Akira Nishiyama ◽  
Takatomi Shokoji ◽  
Li Yao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Reperfusion Injury ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion

scholarly journals Up-regulation of glomerular COX-2 by angiotensin II: Role of reactive oxygen species

2005 ◽  
Vol 68 (5) ◽  
pp. 2143-2153 ◽  
Author(s):  
Edgar A. Jaimes ◽  
Run-Xia Tian ◽  
Damien Pearse ◽  
Leopoldo Raij
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cox 2
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