TY - JOUR
T1 - Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage
AU - Wakisaka, Yoshinobu
AU - Miller, Jordan D.
AU - Chu, Yi
AU - Baumbach, Gary L.
AU - Wilson, Saul
AU - Faraci, Frank M.
AU - Sigmund, Curt D.
AU - Heistad, Donald D.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/6/30
Y1 - 2008/6/30
N2 - We have developed an experimental model of spontaneous intracranial hemorrhage (ICH) in transgenic mice expressing human renin and human angiotensinogen (R+/A+) treated with high-salt diet and Nω- nitro-L-arginine methyl ester (L-NAME). We investigated whether oxidative stress is associated with spontaneous ICH in R+/A+ mice. R+/A+ mice on high-salt diet and L-NAME presented neurologic signs 57±13 (mean±s.e.m.) days after the start of treatment. Intracranial hemorrhage was shown with histologic examination. Levels of superoxide in brain homogenate were significantly increased in R+/A+ mice with ICH (118±10 RLU per sec per mg; RLU, relative light unit) compared with age-matched control mice (19±1) and R+/A+ mice without ICH (53±3). NAD(P)H oxidase activity was significantly higher in R+/A+ mice with ICH (34,933±2,420 RLU per sec per mg) than in control mice (4,984±248) and R+/A+ mice without ICH (15,069±917). These results suggest that increased levels of superoxide are due, at least in part, to increased NAD(P)H oxidase activity. Increased NAD(P)H oxidase activity preceded signs of ICH, and increased further when R+/A+ mice developed ICH. These findings suggest that oxidative stress may contribute to spontaneous ICH in chronic hypertension.
AB - We have developed an experimental model of spontaneous intracranial hemorrhage (ICH) in transgenic mice expressing human renin and human angiotensinogen (R+/A+) treated with high-salt diet and Nω- nitro-L-arginine methyl ester (L-NAME). We investigated whether oxidative stress is associated with spontaneous ICH in R+/A+ mice. R+/A+ mice on high-salt diet and L-NAME presented neurologic signs 57±13 (mean±s.e.m.) days after the start of treatment. Intracranial hemorrhage was shown with histologic examination. Levels of superoxide in brain homogenate were significantly increased in R+/A+ mice with ICH (118±10 RLU per sec per mg; RLU, relative light unit) compared with age-matched control mice (19±1) and R+/A+ mice without ICH (53±3). NAD(P)H oxidase activity was significantly higher in R+/A+ mice with ICH (34,933±2,420 RLU per sec per mg) than in control mice (4,984±248) and R+/A+ mice without ICH (15,069±917). These results suggest that increased levels of superoxide are due, at least in part, to increased NAD(P)H oxidase activity. Increased NAD(P)H oxidase activity preceded signs of ICH, and increased further when R+/A+ mice developed ICH. These findings suggest that oxidative stress may contribute to spontaneous ICH in chronic hypertension.
UR - http://www.scopus.com/inward/record.url?scp=44349143538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44349143538&partnerID=8YFLogxK
U2 - 10.1038/jcbfm.2008.7
DO - 10.1038/jcbfm.2008.7
M3 - Article
C2 - 18301433
AN - SCOPUS:44349143538
VL - 28
SP - 1175
EP - 1185
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 6
ER -