World Journal of Urology

, Volume 26, Issue 6, pp 603–609 | Cite as

The nitric oxide pathway in the human prostate: clinical implications in men with lower urinary tract symptoms

  • George T. Kedia
  • Stefan Ückert
  • Udo Jonas
  • Markus A. Kuczyk
  • Martin Burchardt
Topic Paper


To date, there is an increasing interest in the nitric oxide (NO) pathway as a potential pharmacological target to treat male lower urinary tract symptomatology (LUTS). In the transition zone of the human prostate, a dense nitrinergic innervation has been shown of the fibromuscular stroma, glandular epithelium and blood vessels. The expression of key proteins of the NO pathway, such as the endothelial and neuronal nitric oxide synthase (eNOS, nNOS), cGMP-degrading phosphodiesterase type 5 (PDE5) and cGMP-binding protein kinase (cGK), has also been demonstrated. The hypothesis that an impaired NO/cGMP-signaling may contribute to the pathophysiology of benign prostatic hyperplasia (BPH) is supported by the results from randomized, placebo-controlled clinical studies, indicating that NO donor drugs and PDE5-inhibitors sildenafil, tadalafil and vardenafil may be useful to treat storage and voiding dysfunctions resulting from LUTS in men. Thus, given a potential role of the NO-pathway in the prostate and/or in other parts of lower urinary tract (e.g. bladder), the enhancement of the NO signaling by NO donor drugs, PDE5 inhibitors or activators of the soluble guanylyl cyclase (sGC) may represent a new therapeutic strategy for the treatment of LUTS. This review serves to focus on the role of NO and the NO-dependent signaling in the control of smooth muscle function in the human prostate. Results from clinical trials in men with LUTS/BPH are also discussed.


Prostate BPH LUTS Nitric oxide (NO) Nitric oxide synthase (NOS) Cyclic GMP Phosphodiesterase (PDE) isoenzymes PDE inhibitors 


Conflict of interest statement

There is no conflict of interest.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • George T. Kedia
    • 1
    • 2
  • Stefan Ückert
    • 1
    • 2
  • Udo Jonas
    • 1
  • Markus A. Kuczyk
    • 1
  • Martin Burchardt
    • 1
  1. 1.Division of Surgery, Department of UrologyHannover Medical SchoolHannoverGermany
  2. 2.Urological Research UnitInstitute for Biochemical Research and AnalysesHannoverGermany

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