PMID- 16456123
OWN - NLM
STAT- MEDLINE
DCOM- 20060323
LR  - 20161122
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 37
IP  - 3
DP  - 2006 Mar
TI  - Peroxynitrite diminishes myogenic activity and is associated with decreased 
      vascular smooth muscle F-actin in rat posterior cerebral arteries.
PG  - 894-9
AB  - BACKGROUND AND PURPOSE: This study investigated the effect of peroxynitrite 
      (ONOO-) on pressure-induced myogenic activity and vascular smooth muscle (VSM) 
      actin of isolated posterior cerebral arteries (PCAs). METHODS: Histochemical 
      staining of nitrotyrosine (NT) was used to demonstrate the presence of ONOO- in 
      the cerebrovasculature after 1 hour of middle cerebral artery occlusion with 30 
      minutes of reperfusion. To determine the effect of ONOO- on pressure-induced 
      myogenic activity, third-order PCAs from nonischemic animals were isolated and 
      mounted in an arteriograph chamber. Diameter in response to changes in pressure 
      was determined in the absence and presence of ONOO- (10(-8) to 10(-4) mol/L). 
      Filamentous actin (F-actin) and globular actin (G-actin) were quantified using 
      confocal microscopy in PCAs with and without exposure to ONOO-. RESULTS: NT 
      staining of vascular cells was greater in ischemic brain versus sham animals 
      (56+/-3% versus 35+/-3%; P<0.01). Addition of low concentrations of ONOO- (< or 
      =10(-6) mol/L) to isolated PCAs caused constriction from 129+/-16 microm to 
      115+/-15 microm (P<0.01), whereas concentrations >10(-6) mol/L caused dilation of 
      spontaneous tone and loss of myogenic activity in the physiological range of 50 
      to 125 mm Hg, increasing diameter from 130+/-6 to 201+/-5 microm at 75 mm Hg 
      (P<0.01). In addition, the diminished myogenic activity was associated with a 
      4.5-fold decrease in F-actin content of VSM and a 27% increase in G-actin content 
      (P<0.01). CONCLUSIONS: This study demonstrates that ONOO- affects the myogenic 
      activity of cerebral arteries and causes F-actin depolymerization in VSM, a 
      consequence that could promote vascular damage during reperfusion injury and 
      further brain injury.
FAU - Maneen, Matthew J
AU  - Maneen MJ
AD  - Department of Neurology, University of Vermont, Burlington, VT 05405, USA.
FAU - Hannah, Rachael
AU  - Hannah R
FAU - Vitullo, Lisa
AU  - Vitullo L
FAU - DeLance, Nicole
AU  - DeLance N
FAU - Cipolla, Marilyn J
AU  - Cipolla MJ
LA  - eng
GR  - R01 NS043316/NS/NINDS NIH HHS/United States
GR  - R01 NS40071/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060202
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Actins)
RN  - 0 (Reactive Oxygen Species)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Actins/*metabolism
MH  - Animals
MH  - Blood Pressure
MH  - Brain/pathology
MH  - Cerebral Arteries/*pathology
MH  - Humans
MH  - Infarction, Middle Cerebral Artery
MH  - Ischemia/pathology
MH  - Male
MH  - Microscopy, Confocal
MH  - Muscle, Smooth, Vascular/*drug effects/*metabolism/pathology
MH  - Peroxynitrous Acid/metabolism/*pharmacology
MH  - Posterior Cerebral Artery/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species
MH  - Reperfusion Injury
MH  - Time Factors
MH  - Tyrosine/analogs & derivatives/pharmacology
EDAT- 2006/02/04 09:00
MHDA- 2006/03/24 09:00
CRDT- 2006/02/04 09:00
PHST- 2006/02/04 09:00 [pubmed]
PHST- 2006/03/24 09:00 [medline]
PHST- 2006/02/04 09:00 [entrez]
AID - 01.STR.0000204043.18592.0d [pii]
AID - 10.1161/01.STR.0000204043.18592.0d [doi]
PST - ppublish
SO  - Stroke. 2006 Mar;37(3):894-9. doi: 10.1161/01.STR.0000204043.18592.0d. Epub 2006 
      Feb 2.