Consistent with our findings, it has been reported that cGC and cGMP levels and PKG activity are lowered in the lungs of mice with tobacco smoke-induced pulmonary emphysema25, that eNOS and sGC levels are reduced in the lungs of patients with COPD25,26, that long-term treatment with either sGC stimulators, inorganic nitrite, or l-arginine prevents pulmonary emphysema induced by tobacco smoke or elastase in mice or pigs11,27,28, and that long-term treatment with the sGC stimulator riociguat decreases airway resistance in patients with COPD and pulmonary hypertension29. Here, NOS3 is linked to pulmonary emphysema.