Tetrahydrobiopterin and endothelial function.

Tetrahydrobiopterin is an essential co-factor required for catalytic activity of nitric oxide synthases. A close link between tetrahydrobiopterin and nitric oxide synthesis has been recently demonstrated in a number of different cell types, including endothelial cells. The precise role of tetrahydrobiopterin in regulation of nitric oxide synthase activity is not completely understood; however, it may function as both an allosteric and redox co-factor. In peripheral and cerebral arteries, administration of tetrahydrobiopterin can stimulate production of nitric oxide. By contrast, in arteries depleted of tetrahydrobiopterin, nitric oxide production is impaired. Evidence indicates that, under certain pathological conditions, decreased availability of tetrahydrobiopterin may be responsible for a dysfunction of nitric oxide synthase leading to a shift in the balance between the production of protective nitric oxide and deleterious oxygen-derived free radicals. This concept may have important implications in understanding the mechanisms of endothelial dysfunction and oxidative vascular injury described in a number of vascular diseases, including atherosclerosis. This review will discuss the complex interaction between tetrahydrobiopterin and nitric oxide synthase and its role in the control of vascular tone.