SGCB and pulmonary arterial hypertension: In PAH, endogenous NO synthesis may be reduced for coexistent endothelial dysfunction; therefore, phosphodiesterase-5 inhibition (PDE5i), mediated by PDE5 inhibitors, may be insufficient in cGMP signaling stimulation, which can be more effectively obtained with Riociguat, which can directly stimulate sGC [70].