Role of nitric oxide in a toxin-induced model of haemolytic uraemic syndrome

The role of nitric oxide in the pathogenesis of glomerular thrombotic micro angiopathy was explored using an established rat model in which ricin with or without lipopolysaccharide induced glomerular thrombosis. Ricin alone ca used a small rise in the plasma concentration of nitric oxide (control 9.2/-0.7 mu M, ricin 23.3+/-6.3 mu M 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 mi homogenate, ricin 7.52+/-1.8 pmol/min per ml homog enate, total activity). When ricin and lipopolysaccharide were administered together, calcium-independent NOS activity increased whereas calcium-depen dent activity decreased (1.22+/-12.6 pmol/min per ml homogenate). The incre ase in calcium-independent NOS activity correlated with a high plasma conce ntration of interleukin-1 beta 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.