PTERIDINE AND NITRITE NITRATE FORMATION IN EXPERIMENTAL SEPTIC AND TRAUMATIC SHOCK/

Bacterial lipopolysaccharides (LPS) induce the activity of guanosine t riphosphate (GTP)-cyclohydrolase I (GTP-CHI), the first enzyme in the biosynthesis of tetrahydrobiopterin (H(4)bip) from GTP in endothelial cells and macrophages. In these and other cells, LPS also acts costimu latory with cytokines, i.e., mainly tumor necrosis factor-alpha (TNF-a lpha), H(4)bip is the cofactor for nitric oxide synthase (NOS), We wer e interested in comparing the pteridine and nitrate levels in two babo on models: a hyperdynamic sepsis model and a hemorrhagic traumatic sho ck model. Our results show a similar response of pteridines (H(4)bip, neopterin) and nitrite/nitrate levels to an immune stimulus, LPS, whic h peaks rapidly, induces a sustained increase in pteridine levels in s eptic animals. Since hemorrhagic animals show very little response in terms of cytokine production, it was not possible to measure the induc tion of neopterin and nitrite/nitrate. This information could aid our understanding of the regulatory mechanisms in various forms of experim ental shock.