Chronic hypoxia inhibits tetrahydrobiopterin-induced NO production in rat lungs

► Tetrahydrobiopterin (BH4) increases lung NO production. ► BH4 inhibits hypoxic pulmonary vasoconstriction and the responsiveness of hypoxic rats to BH4 is lower than that of normoxic rats. ► NOS uncoupling due to BH4 oxidation plays a role in chronic hypoxia. ► Inducible NO synthase (iNOS) appears to be the main source of exhaled NO in rats.