PDE5A and chronic thromboembolic pulmonary hypertension: Furthermore, a reduction in endogenous PDE5 activity may explain that PDE5 -inhibition is less effective for treatment of CTEPH and underlines the importance of intervening more upstream in the NO-pathway either by administering NO (75) or stimulating soluable guanylyl cyclase (sGC) by Riociguat, which has recently been approved for therapeutic use in CTEPH (35, 76–78).