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Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...

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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
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Nitric oxide synthase gene transfer for erectile dysfunction in a rat model.

M B Chancellor1, S Tirney, C E Mattes

  • 1Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. chancellormb@msx.upmc.edu

BJU International
|April 18, 2003
PubMed
Summary

Gene therapy using myoblast-mediated delivery of inducible nitric oxide synthase (iNOS) effectively improved erectile function in rats. This approach shows promise for treating erectile dysfunction by enhancing penile smooth muscle relaxation.

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Area of Science:

  • Urology
  • Gene Therapy
  • Molecular Biology

Background:

  • Nitric oxide (NO) is crucial for penile erection, mediating smooth muscle relaxation.
  • Dysregulation of NO pathways can contribute to erectile dysfunction.

Purpose of the Study:

  • To investigate if over-expressing inducible nitric oxide synthase (iNOS) in the corpus cavernosum improves erectile function.
  • To compare the efficacy of different gene delivery methods for iNOS.

Main Methods:

  • Adult Sprague-Dawley rats received injections of plasmid, adenovirus, or adenovirus-transduced myoblast cells (adeno-myoblasts) encoding iNOS or beta-galactosidase into the corpus cavernosum.
  • Intracavernosal pressure (ICP) was measured basally and after cavernosal nerve stimulation.
  • Beta-galactosidase expression and NO release were assessed.

Main Results:

  • All delivery methods showed beta-galactosidase expression, with adeno-myoblasts yielding the highest staining.
  • iNOS-treated rats (adenovirus and adeno-myoblast) exhibited significantly increased basal ICP (55 cmH2O) compared to naive rats (5 cmH2O).
  • Cavernosal nerve stimulation doubled ICP in iNOS-treated animals, and adeno-myoblast delivery resulted in measurable NO release.

Conclusions:

  • Myoblast-mediated gene therapy is a feasible and effective method for delivering iNOS to the corpus cavernosum, surpassing direct adenovirus injection and plasmid transfection.
  • This gene therapy approach holds potential for treating erectile dysfunction.
  • Careful control of iNOS expression is necessary to avoid complications like priapism.