Developmental and spinal cord injury-induced changes in nitric oxide-mediated inhibition in rat urinary bladder

Neurourol Urodyn. 2011 Nov;30(8):1666-74. doi: 10.1002/nau.21143. Epub 2011 Jun 29.


Aims: During postnatal development large amplitude spontaneous activity of the neonatal rat bladder changes to a low amplitude adult pattern of activity that leads to improved storage function. Previously, we have shown that spontaneous activity in neonatal rat bladder strips is inhibited by activation of the nitric oxide (NO)-cGMP signaling pathway. In the present experiments we determined if this inhibitory pathway is altered during postnatal development or spinal cord injury.

Methods: Baseline tone and amplitude and frequency of spontaneous contractions were measured in bladder strips from male or female neonatal (days 10-21), juvenile (days 24-39) and adult female spinal cord intact or chronic spinal cord injured Sprague-Dawley rats.

Results: The inhibitory effects of an NO donor (SNAP) and a PDE-5 inhibitor (zaprinast) on spontaneous activity of bladder strips decreased during postnatal development, while an inhibitory effect of 8-bromo-cGMP, which was blocked by a protein kinase G inhibitor, was detected at all ages tested. However, the effect of NO-cGMP signaling to reduce baseline tone emerged during postnatal development. The inhibition induced by the NO donor was blocked by an inhibitor of soluble guanylyl cyclase (sGC). Chronic spinal cord injury (cSCI), which causes the re-emergence of a neonatal-like pattern of spontaneous activity, did not restore sensitivity to NO-mediated inhibition in adult rat bladders.

Conclusions: These data indicate that while cGMP signaling inhibits activity in young and adult bladders as well as after cSCI, there is a developmental decrease in the sensitivity of bladder to NO-mediated inhibition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Disease Models, Animal
  • Female
  • Guanylate Cyclase / antagonists & inhibitors
  • Guanylate Cyclase / metabolism
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Phosphodiesterase 5 Inhibitors / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction* / drug effects
  • Soluble Guanylyl Cyclase
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / physiopathology
  • Urinary Bladder / drug effects
  • Urinary Bladder / growth & development
  • Urinary Bladder / metabolism*
  • Urinary Bladder / physiopathology
  • Urodynamics* / drug effects


  • Nitric Oxide Donors
  • Phosphodiesterase 5 Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, Cytoplasmic and Nuclear
  • Nitric Oxide
  • Cyclic GMP-Dependent Protein Kinases
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Cyclic GMP