Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission

N Engl J Med. 1992 Jan 9;326(2):90-4. doi: 10.1056/NEJM199201093260203.


Background: Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons.

Methods: We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide.

Results: Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The addition of excess L-arginine, but not D-arginine, largely reversed these inhibitory effects. The specific liberation of nitric oxide (by S-nitroso-N-acetylpenicillamine) caused rapid, complete, and concentration-dependent relaxation of the corpus cavernosum. The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (M&B 22,948). Relaxation was inhibited by methylene blue, which inhibits cyclic GMP synthesis.

Conclusions: Our findings support the hypothesis that nitric oxide is involved in the nonadrenergic, noncholinergic neurotransmission that leads to the smooth-muscle relaxation in the corpus cavernosum that permits penile erection. Defects in this pathway may cause some forms of impotence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Arginine / pharmacology
  • Cyclic GMP / antagonists & inhibitors
  • Electric Stimulation
  • Erectile Dysfunction / physiopathology
  • Humans
  • Male
  • Methylene Blue / pharmacology
  • Middle Aged
  • Muscle Relaxation / physiology*
  • Muscle, Smooth / physiology
  • Nitric Oxide* / metabolism
  • Nitroarginine
  • Organ Culture Techniques
  • Penile Erection / drug effects
  • Penile Erection / physiology*
  • Penis / innervation*
  • Penis / physiology
  • Purinones / pharmacology
  • Synaptic Transmission


  • Purinones
  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • zaprinast
  • Cyclic GMP
  • Methylene Blue