INDUCTION OF GTP CYCLOHYDROLASE-I BY BACTERIAL LIPOPOLYSACCHARIDE IN THE RAT

A 2- to 3-fold increase of GTP cyclohydrolase I (E.C. 3.5.4.16), the k ey enzyme of tetrahydrobiopterin biosynthesis from GTP, was observed i n cerebellum, remaining brain, liver, spleen, and adrenal gland of rat s treated with a single dose of lipopolysaccharide (LPS). This led to increased biopterin levels in tissues but not in plasma. Parallel indu ction of nitric oxide (NO) synthase was indicated by a 10- to 100-fold increase of plasma nitrate levels 6 and 12 hours after injection of L PS. Furthermore, systolic blood pressure was reduced significantly by 23%. Our results demonstrate induction of tetrahydrobiopterin biosynth esis after LPS treatment in vivo.