Referenced in: none

Automatically associated channels: Kir2.3

Title: Peroxynitrite diminishes myogenic tone in cerebral arteries: role of nitrotyrosine and F-actin.

Authors: Matthew J Maneen, Marilyn J Cipolla

Journal, date & volume: Am. J. Physiol. Heart Circ. Physiol., 2007 Feb , 292, H1042-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17040976

Abstract
This study investigated the effect of peroxynitrite (OONO(-))-induced nitrosylation of filamentous (F)-actin on myogenic tone in isolated and pressurized posterior cerebral arteries (PCAs). Immunohistochemical staining was used to determine 3-nitrotyrosine (NT) and F-actin content in vascular smooth muscle after exposure to 10(-7) M or 10(-4) M OONO(-) for 5 or 60 min in isolated third-order PCAs (n = 37) from male Wistar rats pressurized to 75 mmHg in an arteriograph chamber, quantified with confocal microscopy. Additionally, the role of K(+) channels in OONO(-)-induced dilation was investigated with 3 microM glibenclamide or 10 mM tetraethylammonium chloride before OONO(-) exposure. OONO(-) (10(-4) M) induced a 40% dilation of tone (P < 0.05) while diminishing F-actin content by half (P < 0.05) and causing a 60-fold increase in NT (P < 0.05) in the vascular smooth muscle of PCAs. Additionally, F-actin was inversely correlated with both diameter and NT content (P < 0.05) and was significantly colocalized in the vascular smooth muscle with NT (overlap coefficient = 0.8). The dilation to ONOO(-) was independent of K(+) channel activity and thiol oxidation as glibenclamide, tetraethylammonium chloride, and dithiothreitol had no effect on OONO(-)-induced dilation or F-actin or NT content in PCAs. Because NT was colocalized with F-actin, we hypothesize that OONO(-) induces nitrosylation of F-actin in vascular smooth muscle leading to depolymerization and the subsequent loss of myogenic tone, which may promote vascular damage during oxidative stress such as in ischemia and reperfusion injury.