PDE5A and Cirrhosis: In the context of cirrhosis, the synthesis of NO by endothelial cells is diminished, leading to a reduction in cyclic guanosine monophosphate (cGMP) production, which is subsequently degraded to 5′-guanosine monophosphate (5′-GMP) by hyperactive phosphodiesterase-5 (PDE-5) [264,265].