title: Role of nitric oxide in a toxin-induced model of haemolytic uraemic syndrome.
abstract: The role of nitric oxide in the pathogenesis of glomerular thrombotic microangiopathy was explored using an established rat model in which ricin with or without lipopolysaccharide induced glomerular thrombosis. Ricin alone caused a small rise in the plasma concentration of nitric oxide (control 9.2+/-0.7 microM, ricin 23.3+/-6.3 microM at 7 h). This increase occurred after the development of glomerular thrombosis. Nitric oxide synthase (NOS) activity in the kidney showed no significant change from control values (control 5.66+/-2.7 pmol/min per ml homogenate, ricin 7.52+/-1.8 pmol/min per ml homogenate, total activity). When ricin and lipopolysaccharide were administered together, calcium-independent NOS activity increased whereas calcium-dependent activity decreased (1.22+/-2.6 pmol/min per ml homogenate). The increase in calcium-independent NOS activity correlated with a high plasma concentration of interleukin-1beta in the ricin plus lipopolysaccharide group (4,036.83+/-1,001.5 pg/ml). These data indicate that thrombus formation in a rat model of haemolytic uraemic syndrome is independent of the effects of nitric oxide.
authors.affiliation: Renal Research, Clinical Research Block, Queen Elizabeth Hospital, Birmingham, UK. J.M.Williams.MED@bham.ac.uk
authors.forename: J M
authors.initials: JM
authors.lastname: Williams
authors.forename: C J
authors.initials: CJ
authors.lastname: Lote
authors.forename: A
authors.initials: A
authors.lastname: Thewles
authors.forename: J A
authors.initials: JA
authors.lastname: Wood
authors.forename: A J
authors.initials: AJ
authors.lastname: Howie
authors.forename: M C
authors.initials: MC
authors.lastname: Williams
authors.forename: D A
authors.initials: DA
authors.lastname: Adu
authors.forename: C M
authors.initials: CM
authors.lastname: Taylor
mesh_terms: D000818:Animals; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004338:Drug Combinations; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced* / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012276:Ricin
chemical_list: D018925:Chemokines; D016207:Cytokines; D004338:Drug Combinations; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D012276:Ricin