title: Increased nitric oxide inactivation by reactive oxygen species in lead-induced hypertension.
abstract: BACKGROUND
  We have recently found evidence for increased reactive oxygen species (ROS) in rats with lead-induced hypertension. We hypothesized that increased ROS activity may contribute to hypertension by enhancing inactivation of nitric oxide (NO) in this model.
  
  
  METHODS
  Rats were treated for 12 weeks with either lead acetate (100 p.p.m.) alone (Pb group) or lead acetate plus vitamin E-fortified food (5000 U/kg rat chow, Pb + E group). The control animals were fed either regular rat chow or a vitamin E-fortified diet. Blood pressure, creatinine clearance, and urinary excretion of stable NO metabolites (NOx) were monitored, and plasma and tissue abundance of nitrotyrosine, which is the footprint of NO oxidation by ROS, were determined.
  
  
  RESULTS
  The Pb group showed a marked rise in blood pressure, a significant increase in plasma and kidney, heart, liver, and brain nitrotyrosine abundance, and a substantial fall in urinary NOx excretion. Concomitant administration of high-dose vitamin E in the Pb + E group ameliorated hypertension and normalized both urinary NOx excretion and tissue nitrotyrosine without altering tissue lead content. However, vitamin E supplementation had no discernible effect on either blood pressure or nitrotyrosine abundance in the normal controls.
  
  
  CONCLUSIONS
  These findings point to enhanced ROS-mediated inactivation and sequestration of NO, which can potentially contribute to hypertension, tissue damage, and reduced urinary NOx excretion in rats with lead-induced hypertension. The beneficial effects of high-dose vitamin E on blood pressure, tissue nitrotyrosine burden, and urinary NOx excretion support the role of increased ROS activity in the pathogenesis of these abnormalities in this model.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, USA. tabotten@uci.edu
authors.forename: N D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: K
authors.initials: K
authors.lastname: Liang
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D006977:Hypertension, Renal / Q000139:chemically induced* / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000633:toxicity; D007855:Lead Poisoning / Q000150:complications / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009585:Nitrogen Dioxide / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014810:Vitamin E; D007854:Lead; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D009585:Nitrogen Dioxide