In an experimental study on mesenteric arteries of ageing mice, a treatment with exogenous tetrahydrobiopterin increased endothelium-dependent vasodilation and reduced eNOS-derived superoxide formation, confirming an important role of tetrahydrobiopterin and e-NOS uncoupling in age-related endothelial dysfunction [18,19]. This evidence concerns the gene NOS3 and endothelial dysfunction.