Identification of neuronal nitric oxide synthase (nNOS) in human penis: a potential role of reduced neuronally-derived nitric oxide in erectile dysfunction.

Erectile dysfunction (ED) commonly occurs in approximately 15% of men over 70 years old. A number of causes of this condition are recognised with the major mechanism of ED being an impaired relaxation of the corpus cavernosum (CC) smooth muscle and resulting reduction in penile blood flow. There are reports that ED is associated with a reduction in local levels of endothelium-derived nitric oxide (NO) with most studies focussing on the potential role of endothelial nitric oxide synthase (eNOS) in the erectile process. Since there is a recognised neurogenic component of ED we have studied altered nerve density and neuronal nitric oxide synthase (nNOS) distribution by immunohistochemistry and nNOS protein expression by western blot analysis in penises from patients with neurogenic ED and diabetes compared with control tissue obtained from patients undergoing gender reassignment. There was a significant reduction in nerve density in tissue from ED compared with control patients (P < 0.05). Immunostaining for nNOS colocalised with nerves and was reduced in ED tissue, as were nNOS protein levels. We have shown that nerve degeneration observed in penile tissue from ED patients is accompanied by a decrease in nNOS suggesting that reduced neuronal- as well as endothelium-derived NO plays a role in this condition.