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Cited by 1,006Sexual function and dysfunction studiesNitric Oxide and Endothelin EffectsUrinary Bladder and Prostate Research

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

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Rajfer, Jacob, Aronson, William J., Bush, Peggy A., Dorey, Frederick J., Ignarro, Louis J.·1992·New England Journal of Medicine
DOI 10.1056/nejm199201093260203
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Abstract

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.

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  • NO synthesized by NOS in the endothelium diffuses into the vessel wall, activates soluble guanylate cyclase in vascular smooth muscle, raises cyclic GMP, and elicits relaxation of the vessel.

    “NO synthesized by NOS in the endothelium diffuses into the vessel wall where it activates sGC in vascular smooth muscle; this leads to a rise in cyclic GMP (cGMP) and elicits relaxation of the vessel [96-102].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [99]

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2 of the 30 references couldn’t be matched to a known paper.

Research works printed but not linked: 8

  1. [4]4. Lue TF, Hricak H, Schmidt RA, Tanagho EA. Functional evaluation of prnrn vo end s o s ol 1986;135:479-82.
  2. [7]7. Fournier GR Jr, Juenemann K, Lue TF, Tanagho EA. Mechanisms of venoete oen e ie i n ii oe oso J Urol 1987;137:163-7.
  3. [8]8. Saenz de Tejada I, Blanco R, Goldstein I, et al. Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue. Am J Physiol 1988;254:H459-H467.
  4. [12]12. Andersson PO, Bloom SR, Mellander S. Haemodynamics of pelvic nerve -inae at e ote sod e e oie ptes tinal polypeptide. J Physiol 1984;350:209-24.
  5. [15]15. Barnes CD, Eltherington LG. Drug dosage in laboratory animals: a handbook. Berkeley: University of California Press, 1965:261.
  6. [20]20. Dixon WJ, ed. BMDP statistical software manual. Vol. 2. Berkeley: University of California Press, 1990.
  7. [24]24. Gruetter CA, Barry BK, McNamara DB, Gruetter DY, Kadowitz PJ, Ignarro LJ. Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. J Cyclic Nucleotide Res 1979;5:211-24.
  8. [30]30. Ignarro LJ, Bush PA, Buga GM, Rajfer J. Neurotransmitter identity in doubt. Nature 1990;347:131-2. - I. oal l l ad l d t ait oo cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol 1985;25:171-91.

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Authors
Rajfer, J., Aronson, W. J., Bush, P. A., Dorey, F. J., & Ignarro, L. J.
Affiliations
University of California, Los Angeles (US)
ORCID
Aronson, William J.
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1992-01-09
Volume
326
Issue
2
Pages
90-94
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199201093260203
OpenAlex
W2056147576
Cited by
1,006
References
30
Citations by year
2026: 4 · 2025: 8 · 2024: 5 · 2023: 11 · 2022: 12 · 2021: 11 · 2020: 13 · 2019: 14 · 2018: 15 · 2017: 17 · 2016: 17 · 2015: 17 · 2014: 26 · 2013: 22 · 2012: 30
FWCI
50.38
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl040922-11, 5r01hl035014-12)
  • National Heart, Lung, and Blood Institute (HL-35014, HL 40922)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
Keywords
nitric oxide, corpus cavernosum, penile erection, non-adrenergic non-cholinergic neurotransmission, smooth muscle relaxation, erectile dysfunction, cyclic GMP, L-arginine, methylene blue, penile prosthesis, electrical field stimulation
MeSH terms
Adult, Aged, Arginine, Electric Stimulation, Cyclic GMP, Humans, Erectile Dysfunction, Male, Methylene Blue, Middle Aged, Muscle Relaxation, Muscle, Smooth, Synaptic Transmission, Nitric Oxide, Organ Culture Techniques, Penile Erection, Penis, Purinones, Nitroarginine

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