title: Developmental and spinal cord injury-induced changes in nitric oxide-mediated inhibition in rat urinary bladder.
abstract: OBJECTIVE
  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.
authors: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. dea20@pitt.edu
authors: Debra E
authors: DE
authors: Artim
authors: F Aura
authors: FA
authors: Kullmann
authors: Stephanie L
authors: SL
authors: Daugherty
authors: Evan
authors: E
authors: Bupp
authors: Cassandra L
authors: CL
authors: Edwards
authors: William C
authors: WC
authors: de Groat
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects
chemical_list: D020030:Nitric Oxide Donors; D058986:Phosphodiesterase 5 Inhibitors; D047428:Protein Kinase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP