Sildenafil, recognized by its brand name Viagra, is a medication for erectile dysfunction. Its function relies on enhancing a natural process initiated by the signaling molecule nitric oxide. This interaction facilitates an erection in response to arousal, rather than creating one spontaneously.
The Role of Nitric oxide in an Erection
An erection is a vascular event controlled by the nervous system. It begins with sexual arousal, which causes specialized nerve endings and endothelial cells, which line the blood vessels within the penis, to release nitric oxide (NO). The release of NO is the initial step in this cascade.
Once released, nitric oxide diffuses into the smooth muscle cells that form the walls of the arteries in the corpora cavernosa, the two sponge-like chambers of tissue in the penis. Inside these muscle cells, NO activates an enzyme called guanylate cyclase. This activation leads to the increased production of cyclic guanosine monophosphate (cGMP).
The accumulation of cGMP acts as a secondary messenger, signaling the smooth muscle to relax. This relaxation causes the penile arteries to widen, or vasodilate, increasing blood flow into the corpora cavernosa. As blood rushes in and fills these chambers, the penis becomes firm and erect.
How Viagra Amplifies the Nitric Oxide Pathway
The effects of cGMP are naturally short-lived. An enzyme named phosphodiesterase type 5 (PDE5) is highly concentrated in the penile tissue and is responsible for breaking down cGMP. This degradation causes the smooth muscle cells in the arteries to contract again, reducing blood flow and causing the erection to subside.
Sildenafil, the active ingredient in Viagra, is a selective PDE5 inhibitor. Its molecular structure allows it to act as a competitive binding agent for the PDE5 enzyme. By binding to and blocking PDE5, sildenafil prevents the enzyme from degrading cGMP as quickly as it normally would.
Sildenafil does not create nitric oxide or cGMP. It amplifies and prolongs the effects of cGMP that is produced as a result of nitric oxide release during sexual stimulation. By preserving cGMP levels, sildenafil helps maintain the vasodilation necessary to achieve and sustain an erection.
The Importance of Sexual Stimulation
A common misunderstanding is that taking sildenafil will automatically produce an erection. The medication is only effective when the nitric oxide pathway has been initiated by sexual arousal. Without the mental or physical cues of arousal, the nerves in the penis do not receive the signal to release nitric oxide.
Because sildenafil works by inhibiting the breakdown of cGMP, it requires the presence of cGMP to have any effect. No sexual stimulation means no nitric oxide release, and therefore no production of cGMP for sildenafil to protect from degradation.
Therefore, sexual thoughts, feelings, or direct physical stimulation are necessary for the drug to work. It enhances the natural erectile response rather than inducing an artificial one.
Interactions with Other Nitric Oxide-Related Drugs
Sildenafil’s mechanism also explains its potentially dangerous interactions with other medications that influence the nitric oxide system. Certain drugs, particularly nitrates like nitroglycerin prescribed for angina (chest pain), work by increasing nitric oxide levels or acting as NO donors. This causes widespread vasodilation to improve blood flow to the heart.
When sildenafil is combined with a nitrate medication, the effects are synergistic. The nitrate drug increases the production of cGMP throughout the body’s vascular system, while sildenafil prevents this cGMP from being broken down. This combination leads to an excessive level of vasodilation.
The result can be a sudden and severe drop in systemic blood pressure. This reduction can lead to fainting, shock, or a fatal outcome. For this reason, the concurrent use of sildenafil and nitrate medications is strictly contraindicated.