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They do not directly cause penile erections, however, they affect the response to sexual stimulation. During sexual stimulation, nitric oxide is produced, which then activates cyclic guanosine monophosphate cGMP.
This results in smooth muscle relaxation and increased blood flow. There are several PDE isoenzymes, and PDE-5 is the isoenzyme present in highest concentrations in the smooth muscle of the corpora cavernosum of the penis.
The PDE-5 inhibitors, sildenafil, vardenafil, and tadalafil mimic the structure of cGMP and competitively inhibit its breakdown by PDE-5 in the corpus cavernosum and related vessels, leading to increased dilatation and blood flow.