Published online before print February 2, 2006, doi: 10.1161/01.STR.0000204043.18592.0d
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(Stroke. 2006;37:894.)
© 2006 American Heart Association, Inc.
Original Contributions |
Peroxynitrite Diminishes Myogenic Activity and Is Associated With Decreased Vascular Smooth Muscle F-Actin in Rat Posterior Cerebral Arteries
From the Department of Neurology, University of Vermont, Burlington.
Correspondence to Marilyn J. Cipolla, PhD, University of Vermont Department of Neurology, 89 Beaumont Ave, Given C454, Burlington, VT 05405. 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– (
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).
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.
Key Words: actins • cerebral arteries • peroxynitrous acid • reperfusion injury
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