Tetrahydrobiopterin.

The endothelium plays a pivotal role in vascular physiology through a variety of factors, foremost of which is nitric oxide (NO). However, the biochemical mechanisms leading to reduced NO availability and subsequent endothelial dysfunction are not clearly understood. Tetrahydrobiopterin (BH(4)) is an essential cofactor for endothelial NO synthase. Recent preclinical and clinical studies in patients with cardiovascular risk and disease support the central role of reduced BH(4) availability in decreased NO production. This has led to BH(4) supplementation emerging as a possible therapy for conditions characterized by endothelial dysfunction (eg, hypertension, hypercholesterolemia, diabetes, and vascular disease states), and those caused by smoking and aging. Recent advances in drug formulation of BH(4) now offer the potential for better clinical understanding of endothelial function in human health and disease.