Therefore, we set out to investigate the role of NO–sGC–cGMP signaling in the SUHx model of severe PAH and to evaluate the effects of sGC stimulation by riociguat and of PDE-5 inhibition by sildenafil on pulmonary hemodynamics and vascular remodeling in severe experimental PAH. The gene discussed is PDE5A; the disease is pulmonary arterial hypertension.