PRKG1 and pulmonary arterial hypertension: Likewise, in human trials on HFrEF patients with pulmonary arterial hypertension boosting the sGC-cGMP-PKG signaling pathway, either sGC stimulation (riociguat) [39] or phosphodiesterase-5 inhibition (sildenafil) [40,41] failed to significantly reduce pulmonary arterial pressures and improve hemodynamics.