title: Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage.
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(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.
authors.affiliation: Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Wakisaka
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Miller
authors.forename: Yi
authors.initials: Y
authors.lastname: Chu
authors.forename: Gary L
authors.initials: GL
authors.lastname: Baumbach
authors.forename: Saul
authors.initials: S
authors.lastname: Wilson
authors.forename: Frank M
authors.initials: FM
authors.lastname: Faraci
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
authors.forename: Donald D
authors.initials: DD
authors.lastname: Heistad
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004789:Enzyme Activation; D006973:Hypertension / Q000150:complications* / Q000201:enzymology* / Q000503:physiopathology; D020300:Intracranial Hemorrhages / Q000150:complications* / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D019255:NADPH Oxidases