EDN1 and pulmonary arterial hypertension: Currently, PAH therapies target one or more of three major pathways implicated in disease progression: the nitric oxide (NO) pathway, which includes phosphodiesterase type 5 inhibitors (sildenafil and tadalafil) and soluble guanylyl cyclase stimulators (riociguat); the endothelin-1 (ET-1) pathway, which includes receptor antagonists (bosentan, ambrisentan, and macitentan); and the prostacyclin (PGI2) pathway, which includes prostacyclin analogs (epoprostenol, treprostinil, and iloprost) and the non-prostanoid IP-receptor agonist selexipag (7, 48).