NOS3 and pulmonary arterial hypertension: It is remarkable, however, that all three factors differentially regulated by thrombin are also specific targets for pharmacotherapy of pulmonary arterial hypertension, where the drugs act in the opposite direction of the effects seen in vitro for thrombin: eNOS activation (target for L-arginine), sGC stimulation (target for riociguat), and PDE5 inhibition (target for sildenafil and tadalafil) [22]–[27], [38], [39].