title: Increased reactive oxygen species contributes to kidney injury in mineralocorticoid hypertensive rats.
abstract: Hypertension is associated with increased reactive oxygen species (ROS). Renal ROS production and their effects on renal function have never been investigated in mineralocorticoid hypertensive rats. In this study we hypothesized that increased ROS production in kidneys from deoxycorticosterone (DOCA)-salt rats contributes to adverse renal morphological changes and impaired renal function in DOCA-salt hypertensive rats. We also determined whether ROS-induced renal injury was dependent on blood pressure. DOCA-salt hypertensive rats exhibited a marked increase in blood pressure, renal ROS production, glomerular and tubular lesions, and microalbuminuria compared to sham rats. Treatment of DOCA-salt hypertensive rats with apocynin for 28 days resulted in attenuation of systolic blood pressure and improvement of renal morphology. Renal superoxide level in DOCA-salt rats was 215% of sham-operated rats and it was significantly decreased to 140% with apocynin treatment. Urinary protein level was decreased from 27 +/- 3 mg/day in DOCA-salt hypertensive rats to 9 +/- 2 mg/day. 28 days of Vitamin E treatment also reduced renal injury in regard to urinary protein level and renal morphology but had no effect on blood pressure in DOCA-salt rats. Increased urinary 8-isoprostane, a marker for oxidative stress, in DOCA-salt hypertensive rats (55 +/- 8 ng/day) was diminished by vitamin E treatment (24 +/- 6 ng/day). These data suggest that renal injury characteristic of mineralocorticoid hypertension is associated with oxidative stress and is partly independent of blood pressure.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA, USA. ljin8@jhmi.edu
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.forename: R A
authors.initials: RA
authors.lastname: Beswick
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Palmer
authors.forename: T A
authors.initials: TA
authors.lastname: Taylor
authors.forename: J S
authors.initials: JS
authors.lastname: Pollock
authors.forename: D M
authors.initials: DM
authors.lastname: Pollock
authors.forename: M W
authors.initials: MW
authors.lastname: Brands
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D006651:Histocytochemistry; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000009:adverse effects* / Q000378:metabolism*; D013481:Superoxides / Q000009:adverse effects / Q000032:analysis; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013481:Superoxides; D014810:Vitamin E; D003900:Desoxycorticosterone; C056165:acetovanillone