Peroxynitrite diminishes myogenic activity and is associated with decreased vascular smooth muscle F-actin in rat posterior cerebral arteries

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 mu m to 115 +/- 15 mu m (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 mu m 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.