Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage

Yoshinobu Wakisaka; Jordan D Miller; Yi Chu; Gary L Baumbach; Saul Wilson; Frank M Faraci; Curt D Sigmund; Donald D Heistad

doi:10.1038/jcbfm.2008.7

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Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage

Journal article

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Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage

Yoshinobu Wakisaka, Jordan D Miller, Yi Chu, Gary L Baumbach, Saul Wilson, Frank M Faraci, Curt D Sigmund and Donald D Heistad

Journal of cerebral blood flow and metabolism, Vol.28(6), pp.1175-1185

06/2008

DOI: 10.1038/jcbfm.2008.7

PMCID: PMC3153951

PMID: 18301433

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Abstract

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 ω -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±10RLU 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.

Hypertension

Oxidative Stress

intracranial hemorrhage

Details

Title: Subtitle: Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage
Creators: Yoshinobu Wakisaka - Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Jordan D Miller - Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Yi Chu - Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Gary L Baumbach - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Saul Wilson - Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Frank M Faraci - Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Curt D Sigmund - Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Donald D Heistad - Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Journal of cerebral blood flow and metabolism, Vol.28(6), pp.1175-1185
DOI: 10.1038/jcbfm.2008.7
PMID: 18301433
PMCID: PMC3153951
NLM abbreviation: J Cereb Blood Flow Metab
ISSN: 0271-678X
eISSN: 1559-7016
Grant note: P50 HL055006-08 || HL / National Heart, Lung, and Blood Institute : NHLBI
Language: English
Date published: 06/2008
Academic Unit: Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
Record Identifier: 9984040392702771

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