TETRAHYDROBIOPTERIN AND ENDOTHELIAL FUNCTION

Tetrahydrobiopterin is an essential co-factor required for catalytic a ctivity of nitric oxide synthases. A close link between tetrahydrobiop terin and nitric oxide synthesis has been recently demonstrated in a n umber of different cell types, including endothelial cells. The precis e role of tetrahydrobiopterin in regulation of nitric oxide synthase a ctivity is not completely understood; however, it may function as both an allosteric and a redox co-factor. In peripheral and cerebral arter ies, administration of tetrahydrobiopterin can stimulate production of nitric oxide. By contrast, in arteries depleted of tetrahydrobiopteri n, nitric oxide production is impaired. Evidence indicates that, under certain pathological conditions, decreased availability of tetrahydro biopterin may be responsible for a dysfunction of nitric oxide synthas e leading to a shift in the balance between the production of protecti ve nitric oxide and deleterious oxygen-derived free radicals. This con cept may have important implications in understanding the mechanisms o f endothelial dysfunction and oxidative vascular injury described in a number of vascular diseases, including atherosclerosis. This review w ill discuss the complex interaction between tetrahydrobiopterin and ni tric oxide synthase and its role in the control of vascular tone.