NOS3 and pulmonary arterial hypertension: Dihydrofolate reductase (DHFR) is not a therapeutic intervention point for PAH treatments; rather, it is reported to affect the balance between NO and superoxide production in endothelial cells via endothelial nitric oxide synthase (eNOS) coupling [30], the latter of which is implicated in endothelium-dependent vasodilation [31].