PMID- 23576605
OWN - NLM
STAT- MEDLINE
DCOM- 20130830
LR  - 20211021
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 304
IP  - 12
DP  - 2013 Jun 15
TI  - Angiotensin II slow-pressor hypertension enhances NMDA currents and 
      NOX2-dependent superoxide production in hypothalamic paraventricular neurons.
PG  - R1096-106
LID - 10.1152/ajpregu.00367.2012 [doi]
AB  - Adaptive changes in glutamatergic signaling within the hypothalamic 
      paraventricular nucleus (PVN) may play a role in the neurohumoral dysfunction 
      underlying the hypertension induced by "slow-pressor" ANG II infusion. We 
      hypothesized that these adaptive changes alter production of gp91phox NADPH 
      oxidase (NOX)-derived reactive oxygen species (ROS) or nitric oxide (NO), 
      resulting in enhanced glutamatergic signaling in the PVN. Electron microscopic 
      immunolabeling showed colocalization of NOX2 and N-methyl-D-aspartate receptor 
      (NMDAR) NR1 subunits in PVN dendrites, an effect enhanced (+48%, P < 0.05 vs. 
      saline) in mice receiving ANG II (600 ng.kg(-)(1).min(-)(1) sc). Isolated PVN cells or 
      spinally projecting PVN neurons from ANG II-infused mice had increased levels of 
      ROS at baseline (+40 +/- 5% and +57.6 +/- 7.7%, P < 0.01 vs. saline) and after NMDA 
      (+24 +/- 7% and +17 +/- 5.5%, P < 0.01 and P < 0.05 vs. saline). In contrast, ANG II 
      infusion suppressed NO production in PVN cells at baseline (-29.1 +/- 5.2%, P < 
      0.05 vs. saline) and after NMDA (-18.9 +/- 2%, P < 0.01 vs. saline), an effect 
      counteracted by NOX inhibition. In whole cell recording of unlabeled and spinally 
      labeled PVN neurons in slices, NMDA induced a larger inward current in ANG II 
      than in saline groups (+79 +/- 24% and +82.9 +/- 6.6%, P < 0.01 vs. saline), which 
      was reversed by the ROS scavenger MnTBAP and the NO donor 
      S-nitroso-N-acetylpenicillamine (P > 0.05 vs. control). These findings suggest 
      that slow-pressor ANG II increases the association of NR1 with NOX2 in dendrites 
      of PVN neurons, resulting in enhanced NOX-derived ROS and reduced NO during 
      glutamatergic activity. The resulting enhancement of NMDAR activity may 
      contribute to the neurohumoral dysfunction underlying the development of 
      slow-pressor ANG II hypertension.
FAU - Wang, Gang
AU  - Wang G
AD  - Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY 
      10065, USA. gaw2001@med.cornell.edu
FAU - Coleman, Christal G
AU  - Coleman CG
FAU - Chan, June
AU  - Chan J
FAU - Faraco, Giuseppe
AU  - Faraco G
FAU - Marques-Lopes, Jose
AU  - Marques-Lopes J
FAU - Milner, Teresa A
AU  - Milner TA
FAU - Guruju, Mallikarjuna R
AU  - Guruju MR
FAU - Anrather, Josef
AU  - Anrather J
FAU - Davisson, Robin L
AU  - Davisson RL
FAU - Iadecola, Costantino
AU  - Iadecola C
FAU - Pickel, Virginia M
AU  - Pickel VM
LA  - eng
GR  - R01 HL063887/HL/NHLBI NIH HHS/United States
GR  - R01 HL098351/HL/NHLBI NIH HHS/United States
GR  - HL-096571/HL/NHLBI NIH HHS/United States
GR  - P01 HL084207/HL/NHLBI NIH HHS/United States
GR  - P01 HL096571/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130410
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 11062-77-4 (Superoxides)
RN  - 11128-99-7 (Angiotensin II)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 1.6.3.- (Cybb protein, mouse)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Angiotensin II/*adverse effects/pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Calcium/metabolism
MH  - Hypertension/*chemically induced/*metabolism
MH  - Male
MH  - Membrane Glycoproteins/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron, Transmission
MH  - Models, Animal
MH  - N-Methylaspartate/*metabolism
MH  - NADPH Oxidase 2
MH  - NADPH Oxidases/*metabolism
MH  - Neurons/cytology/metabolism/ultrastructure
MH  - Nitric Oxide/metabolism
MH  - Paraventricular Hypothalamic Nucleus/cytology/*metabolism/ultrastructure
MH  - Patch-Clamp Techniques
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Superoxides/*metabolism
PMC - PMC3680791
OTO - NOTNLM
OT  - NADPH oxidase
OT  - NMDA receptors
OT  - electron microscopy
OT  - nitric oxide
OT  - patch clamp
OT  - reactive oxygen species
EDAT- 2013/04/12 06:00
MHDA- 2013/08/31 06:00
PMCR- 2014/06/15
CRDT- 2013/04/12 06:00
PHST- 2013/04/12 06:00 [entrez]
PHST- 2013/04/12 06:00 [pubmed]
PHST- 2013/08/31 06:00 [medline]
PHST- 2014/06/15 00:00 [pmc-release]
AID - ajpregu.00367.2012 [pii]
AID - R-00367-2012 [pii]
AID - 10.1152/ajpregu.00367.2012 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2013 Jun 15;304(12):R1096-106. doi: 
      10.1152/ajpregu.00367.2012. Epub 2013 Apr 10.