Therefore, we tested whether male hearts were equipped with a PDE5-coupled cGMP regulatory system that is less estrogen dependent. Gender differences in Fildena responses and the mechanism involving eNOS-cGMP synthesis and PKG activation under cardiac stress. (B) PDE5 activity in Gq/oe female hearts subjected to sham operation (non-OVX), OVX, and OVX with E2 replacement (n = 5-8 per group).