Tetrahydrobiopterin, superoxide, and vascular dysfunction.

(6R)-5,6,7,8-Tetrahydrobiopterin (BH(4)) is an endogenously produced pterin that is found widely distributed in mammalian tissues. BH(4) works as a cofactor of aromatic amino acid hydroxylases and nitric oxide synthases. In the vasculature a deficit of BH(4) is implicated in the mechanisms of several diseases including atherosclerosis, hypertension, diabetic vascular disease, and vascular complications from cigarette smoking and environmental pollution. These ill-effects are connected to the ability of BH(4) to regulate reactive oxygen species levels in the endothelium. The possibility of using BH(4) as a therapeutical agent in cardiovascular medicine is becoming more compelling and many biochemical and physiological aspects involved in this application are currently under investigation. This review summarizes our current understanding of BH(4) reactivity and some aspects of cellular production and regulation.