PMID- 17040976
OWN - NLM
STAT- MEDLINE
DCOM- 20070320
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 292
IP  - 2
DP  - 2007 Feb
TI  - Peroxynitrite diminishes myogenic tone in cerebral arteries: role of 
      nitrotyrosine and F-actin.
PG  - H1042-50
AB  - This study investigated the effect of peroxynitrite (OONO(-))-induced 
      nitrosylation of filamentous (F)-actin on myogenic tone in isolated and 
      pressurized posterior cerebral arteries (PCAs). Immunohistochemical staining was 
      used to determine 3-nitrotyrosine (NT) and F-actin content in vascular smooth 
      muscle after exposure to 10(-7) M or 10(-4) M OONO(-) for 5 or 60 min in isolated 
      third-order PCAs (n = 37) from male Wistar rats pressurized to 75 mmHg in an 
      arteriograph chamber, quantified with confocal microscopy. Additionally, the role 
      of K(+) channels in OONO(-)-induced dilation was investigated with 3 microM 
      glibenclamide or 10 mM tetraethylammonium chloride before OONO(-) exposure. 
      OONO(-) (10(-4) M) induced a 40% dilation of tone (P < 0.05) while diminishing 
      F-actin content by half (P < 0.05) and causing a 60-fold increase in NT (P < 
      0.05) in the vascular smooth muscle of PCAs. Additionally, F-actin was inversely 
      correlated with both diameter and NT content (P < 0.05) and was significantly 
      colocalized in the vascular smooth muscle with NT (overlap coefficient = 0.8). 
      The dilation to ONOO(-) was independent of K(+) channel activity and thiol 
      oxidation as glibenclamide, tetraethylammonium chloride, and dithiothreitol had 
      no effect on OONO(-)-induced dilation or F-actin or NT content in PCAs. Because 
      NT was colocalized with F-actin, we hypothesize that OONO(-) induces 
      nitrosylation of F-actin in vascular smooth muscle leading to depolymerization 
      and the subsequent loss of myogenic tone, which may promote vascular damage 
      during oxidative stress such as in ischemia and reperfusion injury.
FAU - Maneen, Matthew J
AU  - Maneen MJ
AD  - Department of Neurology, University of Vermont, 89 Beaumont Ave., Given C454, 
      Burlington, VT 05405, USA.
FAU - Cipolla, Marilyn J
AU  - Cipolla MJ
LA  - eng
GR  - R01 NS043316/NS/NINDS NIH HHS/United States
GR  - R01 NS040071/NS/NINDS NIH HHS/United States
GR  - R01-NS-045940/NS/NINDS NIH HHS/United States
GR  - R01-NS-040071/NS/NINDS NIH HHS/United States
GR  - R01-NS-043316/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 - 20061013
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Actins)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Sulfhydryl Compounds)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 66-40-0 (Tetraethylammonium)
RN  - SX6K58TVWC (Glyburide)
RN  - T8ID5YZU6Y (Dithiothreitol)
SB  - IM
MH  - Actins/*metabolism
MH  - Animals
MH  - Dithiothreitol/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Glyburide/pharmacology
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Male
MH  - Microscopy, Confocal
MH  - Oxidation-Reduction
MH  - Peroxynitrous Acid/*metabolism/pharmacology
MH  - Posterior Cerebral Artery/drug effects/*metabolism
MH  - Potassium Channel Blockers/pharmacology
MH  - Potassium Channels/drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Sulfhydryl Compounds/metabolism
MH  - Tetraethylammonium/pharmacology
MH  - Time Factors
MH  - Tyrosine/*analogs & derivatives/metabolism
MH  - *Vasodilation/drug effects
EDAT- 2006/10/17 09:00
MHDA- 2007/03/21 09:00
CRDT- 2006/10/17 09:00
PHST- 2006/10/17 09:00 [pubmed]
PHST- 2007/03/21 09:00 [medline]
PHST- 2006/10/17 09:00 [entrez]
AID - 00800.2006 [pii]
AID - 10.1152/ajpheart.00800.2006 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H1042-50. doi: 
      10.1152/ajpheart.00800.2006. Epub 2006 Oct 13.