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This signal cascade is attenuated by PDE5 which breaks the phosphodiester bond of cGMP, converting it to GMP. Inhibition of PDE5 by tadalafil increases signaling via the PKG cascade which supports penile smooth muscle relaxation during sexual arousal by decreasing Ca2+ entry into smooth muscle cells. This smooth muscle relaxation allows blood to fill the corpus cavernosum thereby producing an erection. Tadalafil, as a selective PDE-5 inhibitor, has an effect similar to sildenafil and thus it decreases pulmonary hypertension by reducing hypoxic pulmonary vasoconstriction in HAPE (Schmidt, 2015