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

Research output: Contribution to journalArticle

23 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1175-1185
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume28
Issue number6
DOIs
StatePublished - Jun 30 2008

Keywords

  • Hypertension
  • Intracranial hemorrhage
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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    Wakisaka, Y., Miller, J. D., Chu, Y., Baumbach, G. L., Wilson, S., Faraci, F. M., Sigmund, C. D., & Heistad, D. D. (2008). Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage. Journal of Cerebral Blood Flow and Metabolism, 28(6), 1175-1185. https://doi.org/10.1038/jcbfm.2008.7