We hypothesize that improvement in PAH-SSc will only be achieved with therapy directly targeted at RV-PV dysfunction. Sildenafil and tadalafil inhibit phosphodiesterase type 5 (PDE5) which is abundant in the lung and is the main enzyme responsible for cyclic Guanosine MonoPhosphate (cGMP) hydrolysis. The resulting increase in cGMP probably mediates the relaxant and anti-hypertrophic actions of nitric oxide and natriuretic peptides in vascular tissues, and exerts a direct anti-hypertrophic action on cardiac muscle as demonstrated in compelling preliminary experiments by investigators of the NHLBI-funded Hopkins Scientific Center of Clinically Oriented Research (SCCOR) in Pulmonary Vascular Disease. In these experiments, sildenafil was capable of preventing and reversing RV hypertrophy and dysfunction in a model of pulmonary artery banding, similar to its effects on the left ventricle with aortic banding (20), indicating a direct beneficial action on RV remodeling.