Modulation of pulmonary vascular tone by novel analogues of tetrahydrobiopterin

Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS), is a highly polar and unstable molecule, which is subject to autooxidation, which ultimately leads to superoxide production. Novel analogues of BH4, 6-hydroxymethylpterin (HMP) and 6-acetyl-7-dimethyldihydropterin (ADDP), which are radical intermediates having more stable oxidation states, were synthesized. To determine the potential use of the analogues as vasodilatory agents in reducing pulmonary hypertension, we studied their effects on normal pulmonary arteries as well as in pulmonary arteries depleted of endogenous reserves of BH4.