Nitric oxide (NO) is constitutively produced in the lung by NO-synthases. The main cellular sources of lung NO production are the vascular endothelium and the airway epithelia [1, 2]. Adaptation of the perfusion distribution to well ventilated areas of the lung (ventilation/perfusion (V/Q) matching) is mainly regulated by local NO production [3, 4]. NO- synthase activity is regulated on transcriptional and post-translational redox-based modulation level [5]. The common signaling pathway of endogenous vasodilators, such as nitric oxide, prostaglandins, and natriuretic peptides, engage cyclic nucleotides (cAMP and cGMP). The enzymatic source of these second messengers are mainly adenylate-and guanylate-cyclases [6]. PDEs represent a superfamily of enzymes, with PDE1 through PDE11 being currently known, that inactivate cyclic AMP and cyclic GMP, with different tissue distribution and substrate specificities [6, 7]. Depending on their selective profile, PDE inhibitors differentially regulate the activity of cAMP and/or cGMP. Thus, they might be offered as therapeutic tools to augment and prolong prostanoid-and NO-related vascular effects. The efficacy of this approach has been proven in various experimental studies [8, 9]. The most important cyclic GMP degrading phosphodiesterase – PDE5 – is abundantly expressed in lung tissue [7]. The selective PDE5 inhibitor sildenafil has been approved for the treatment of erectile dysfunction [10]. Documented use in numerous otherwise healthy individuals and patients with a variety of underlying diseases sildenafil displayed an excellent safety profile [11].