title: Peroxynitrite diminishes myogenic activity and is associated with decreased vascular smooth muscle F-actin in rat posterior cerebral arteries.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maneen
authors.forename: Rachael
authors.initials: R
authors.lastname: Hannah
authors.forename: Lisa
authors.initials: L
authors.lastname: Vitullo
authors.forename: Nicole
authors.initials: N
authors.lastname: DeLance
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Cipolla
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D002536:Cerebral Arteries / Q000473:pathology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D007511:Ischemia / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology*; D020769:Posterior Cerebral Artery / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000199:Actins; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine