Relaxation of phasic contractile activity of human detrusor strips by cyclic nucleotide phosphodiesterase type 4 inhibition

Eur Urol. 2007 Mar;51(3):772-80; discussion 780-1. doi: 10.1016/j.eururo.2006.10.023. Epub 2006 Oct 25.


Objectives: Detrusor smooth muscle relaxation is mainly mediated by the cyclic adenosine monophosphate (cAMP) pathway. Elevation of cAMP levels by phosphodiesterase type 4 (PDE4) inhibition relaxes smooth muscles of various origins. We aimed to determine the effect of a PDE4 inhibitor, rolipram, on human detrusor contractions.

Methods: Human bladder strips (from 20 different donors) with no known overactive bladder (OAB) were studied in organ baths. Detrusor samples with or without urothelium were incubated with carbachol 10(-6)mol/l (in presence or absence of forskolin, 3.10(-7)mol/l) or with KCl 10mmol/l to enhance phasic contractile activity. Concentration response curves for rolipram or vehicle were then performed.

Results: Rolipram (10(-9) to 3.10(-5)mol/l) induced a moderate relaxing effect on carbachol-induced contractions. This effect was enhanced when cAMP levels were increased by forskolin (the maximal effect was 53.0+/-5.1 vs. 83.1+/-5.7%, p<0.01) or in strips with urothelium. In contrast, rolipram (10(-9) to 10(-4)mol/l) drastically inhibited phasic contractile activity: The developed tension, the area under the curve, and the amplitude of phasic activity were reduced to 64.8+/-3.6, 91.2+/-5.3, and 82.3+/-7.3%, respectively, versus 23.6+/-9.5, 34.7+/-18.8, and 18.0+/-16.2% for vehicle, respectively (p<0.05). Frequency of phasic activity was 0.96+/-0.45 contractions per minute versus 2.6+/-0.18 for vehicle (p<0.001). In strips with urothelium, the inhibitory effect of rolipram on phasic contractile activity was similar.

Conclusions: PDE4 isoenzymes are strongly involved in the regulation of phasic myogenic activity of human bladder strips. Because an increase of this phasic activity may play a role in the pathophysiology of detrusor overactivity, PDE4 inhibitors might represent an attractive strategy for the treatment of OAB.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Muscle Relaxation / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Rolipram / pharmacology*
  • Urinary Bladder / drug effects*
  • Urinary Bladder / physiology*


  • Phosphodiesterase Inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Rolipram