Nitric oxide and penile erectile function

Pharmacol Ther. 2005 May;106(2):233-66. doi: 10.1016/j.pharmthera.2004.11.011. Epub 2005 Mar 2.


The discovery of nitric oxide (NO) as an intercellular messenger or neurotransmitter opened a new era for identifying the important mechanisms underlying physiological and pathophysiological events in autonomically innervated organs and tissues; it also provided the way for development of new therapeutics based on a novel concept of molecule and cell interaction. Endothelium-derived relaxing factor (EDRF) discovered by Furchgott and Zawadzki has been proved to be NO, a labile gaseous molecule, that modulates vascular tone, platelet aggregation and adhesion, and vascular smooth muscle proliferation. Later, NO was determined to act as a non-adrenergic, non-cholinergic (NANC) neurotransmitter of postganglionic parasympathetic nerve fibers, innervating a variety of smooth muscles including the penile corpus cavernosum (CC). The nerve is called "nitrergic" or "nitroxidergic". Although CC sinusoidal endothelial cells also produce and liberate NO in response to chemical and possibly physical stimuli, roles of neurogenic NO in penile erection appear to be more attractive and convincing. NO is formed from L-arginine via catalysis by NO synthase (NOS) isoforms, neuronal (nNOS), endothelial (eNOS), and inducible NOS. NO from nerves and possibly endothelia plays a crucial role in initiating and maintaining intracavernous pressure increase, penile vasodilatation, and penile erection that are dependent on cyclic GMP synthesized with activation of soluble guanylyl cyclase by NO in smooth muscle cells. Erectile dysfunction (ED) is caused by a variety of pathogenic factors, particularly impaired formation and action of NO. Thus, replenishment of this molecule or intracellular cyclic GMP is expected so far to be the most promising therapeutic measures for patients with ED. This article includes recent advances in research on physiological roles and pathophysiological implications of NO in penile erection and on novel therapy for ED in reference to NO.

Publication types

  • Review

MeSH terms

  • Aging / metabolism
  • Aging / physiology
  • Animals
  • Electric Stimulation Therapy
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / physiopathology
  • Erectile Dysfunction / therapy
  • Humans
  • Male
  • Nitrergic Neurons* / drug effects
  • Nitrergic Neurons* / physiology
  • Nitric Oxide / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide / therapeutic use
  • Nitric Oxide Synthase / pharmacology
  • Nitric Oxide Synthase / physiology*
  • Nitric Oxide Synthase Type III
  • Penile Erection / drug effects
  • Penile Erection / physiology*
  • Phosphodiesterase Inhibitors / adverse effects
  • Phosphodiesterase Inhibitors / therapeutic use*


  • Phosphodiesterase Inhibitors
  • Nitric Oxide
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III