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Submitted on December 7, 2005
From the Department of Neurology, University of Vermont, Burlington. * To whom correspondence should be addressed. E-mail: Marilyn.Cipolla{at}uvm.edu.
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- ( 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.
Accepted on December 9, 2005
Peroxynitrite Diminishes Myogenic Activity and Is Associated With Decreased Vascular Smooth Muscle F-Actin in Rat Posterior Cerebral Arteries
Matthew I. Maneen MS;
10-6 mol/L) to isolated PCAs caused constriction from 129±16 µm to 115±15 µm (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 µm 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).
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