Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage. J Cereb Blood Flow Metab 2008 Jun;28(6):1175-85
Date
02/28/2008Pubmed ID
18301433Pubmed Central ID
PMC3153951DOI
10.1038/jcbfm.2008.7Scopus ID
2-s2.0-44349143538 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
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 N(omega)-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.
Author List
Wakisaka Y, Miller JD, Chu Y, Baumbach GL, Wilson S, Faraci FM, Sigmund CD, Heistad DDAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Enzyme Activation
Hypertension
Intracranial Hemorrhages
Male
Mice
Mice, Inbred ICR
Mice, Transgenic
NADPH Oxidases
Oxidative Stress
Superoxides