Nitric oxide (NO) plays a central, scientifically validated role in the physiology of erectile function. The endothelium of blood vessels and nonadrenergic, noncholinergic neurons within the penis produce nitric oxide during sexual stimulation. NO activates the enzyme guanylate cyclase, which increases levels of cyclic guanosine monophosphate (cGMP). Elevated cGMP causes relaxation of smooth muscle in the corpus cavernosum, facilitating increased blood flow and resulting in penile erection.

The critical role of NO in erectile function is the basis for the development of phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil (Viagra), tadalafil, and vardenafil. These medications do not directly provide nitric oxide but rather inhibit the breakdown of cGMP, potentiating the effects of endogenous NO. Clinical studies and reviews (e.g., Burnett, 2006, J Androl; Moncada & Higgs, 2006, Eur Heart J) have consistently shown that impaired NO signaling is a key factor in erectile dysfunction (ED), and enhancing this pathway improves erectile outcomes.

While direct administration of NO gas is not practical, various interventions aim to increase NO bioavailability (e.g., L-arginine supplementation, lifestyle changes). Overall, the scientific evidence for the role of nitric oxide in treating and supporting erectile dysfunction is robust and underpins current first-line pharmacological therapies for ED.