Modulation of nitric oxide synthase activity by ibuprofen

Inhibition of NO synthesis represents a new therapeutical approach in the treatment of inflammation. Clinical use of NOS inhibitors will necessitate the design of drugs selective for iNOS, because inhibition of constitutive endothelial NOS may cause adverse cardiovascular side effects. This study examines the effect of ibuprofen and its stereoeisomeric components on the activation of iNOS and cNOS as well as on the NO production by human umbilical vein endothelial cells. At therapeutic concentrations Ibuprofen activated iNOS and inhibited NOS. In endothelial cell culture experiments activation of NO production was seen especially at supratherapeutic ibuprofen concentrations. Both stereoisomeric components of ibuprofen showed comparable effects. This drug can therefore not be used for the selective inhibition of iNOS.