Peroxynitrite Diminishes Myogenic Activity and Is Associated With Decreased Vascular Smooth Muscle F-Actin in Rat Posterior Cerebral Arteries

Abstract

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.