title: Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome.
abstract: BACKGROUND
  Nitric oxide (NO) is an endogenous vasodilator and platelet inhibitor. An enhanced NO production has been detected in patients with hemolytic uremic syndrome (HUS), although its implication in HUS pathogenesis has not been clarified.
  
  
  METHODS
  A mouse model of Shiga toxin 2 (Stx2)-induced HUS was used to study the role of NO in the development of the disease. Modulation of l-arginine-NO pathway was achieved by oral administration of NO synthase (NOS) substrate or inhibitors, and renal damage, mortality and platelet activity were evaluated. The involvement of platelets was studied by means of a specific anti-platelet antibody.
  
  
  RESULTS
  Inhibition of NO generation by the NOS inhibitor L-NAME enhanced Stx2-mediated renal damage and lethality; this effect was prevented by the addition of l-arginine. The worsening effect of L-NAME involved enhanced Stx2-mediated platelet activation, and it was completely prevented by platelet depletion.
  
  
  CONCLUSIONS
  NO exerts a protective role in the early pathogenesis of HUS, and its inhibition potentiates renal damage and mortality through a mechanism involving enhanced platelet activation.
authors.affiliation: División Medicina Experimental, Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Capital Federal, Buenos Aires, Republica Argentina. colodran@hotmail.com
authors.forename: Graciela I
authors.initials: GI
authors.lastname: Dran
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Fernández
authors.forename: Carolina J
authors.initials: CJ
authors.lastname: Rubel
authors.forename: Emilse
authors.initials: E
authors.lastname: Bermejo
authors.forename: Sonia
authors.initials: S
authors.lastname: Gomez
authors.forename: Roberto
authors.initials: R
authors.lastname: Meiss
authors.forename: Martín A
authors.initials: MA
authors.lastname: Isturiz
authors.forename: Marina S
authors.initials: MS
authors.lastname: Palermo
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005340:Fibrinogen / Q000032:analysis; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects; D022641:Shiga Toxin 2 / Q000633:toxicity*; D013927:Thrombosis / Q000139:chemically induced / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D014508:Urea / Q000097:blood
chemical_list: D004791:Enzyme Inhibitors; D022641:Shiga Toxin 2; D009569:Nitric Oxide; D014508:Urea; D005340:Fibrinogen; D019331:NG-Nitroarginine Methyl Ester