Furthermore, a recent clinical trial of pulmonary arterial hypertension also demonstrated that the combined inhibition of neprilysin and PDE5 increase both plasma NP and cGMP levels and decreased pulmonary vascular resistance without affecting systemic blood pressure (Hobbs et al., 2019), which makes contrast to the concomitant use of PDE5 inhibitor (sildenafil) with sGC stimulator (riociguat) having been reported to be associated with hypotension but without beneficial effects on hemodynamics or exercise capacity (Galiè et al., 2015). The gene discussed is PDE5A; the disease is pulmonary arterial hypertension.