Participation of L-arginine-nitric oxide pathway in the pathogenesis of hemolytic uremic syndrome in a murine model

DRAN G.I; FERNÁNDEZ G.C; RUBEL C.J; BERMEJO E; GOMEZ, S; ISTURIZ M.A.; PALERMO M.S.

KIDNEY INTERNATIONAL

Blackwell Science Ltd

Lugar: USA; Año: 2002 vol. 62 p. 1338 - 1348

0085-2538

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 RUS pathogenesis has not been clarified. Methods. A mouse model of Shiga toxin 2 (Stx2)-induced RUS 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 Stx2­mediated 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.