EDN1 and pulmonary arterial hypertension: Patients with PAH disorder have increased ET-1 levels typically found in the lungs and circulation, thus allowing ET-1 to be a promising treatment target.219–221 The NO pathway is targeted through phosphodiesterase-5 (PDE5) inhibitors, including tadalafil, sildenafil, riociguat and soluble guanylate cyclase (sGC) stimulator.222 Restoring cGMP levels is central to therapy in the NO-sGC-cyclic guanosine monophosphate (cGMP) axis.