Hyaluronic acid ameliorates bladder hyperactivity via the inhibition of H 2O 2-enhanced purinergic and muscarinic signaling in the rat

Chung Hsin Yeh, Han Sun Chiang, Chiang Ting Chien*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Aims: We hypothesize that increased H 2O 2 in the urinary bladder may affect ATP and acetylcholine release and activate urothelial purinergic and muscarinic signaling consequently leading to hyperactive bladder. Materials and Methods: We infused 0.3% and 1.5% H 2O 2 to the urinary bladder to evaluate the voiding function and frequency, pelvic afferent (PANA) and pelvic efferent nerve activity (PENA) simultaneously in the urethane anesthetized rats. We measured ATP and acetylcholine content in the rat urinary bladder under saline or H 2O 2 stimulation. Hyaluronic acid, muscarinic, and purinergic receptor antagonists were used to evaluate their effects and mechanisms on H 2O 2-induced hyperactive bladder. Results: Intravesical H 2O 2 administration increased the frequency of voiding and the maximal amplitude of intravesical pressure (IVP) in the urethane anesthetized rats. Intravesical H 2O 2 decreased the threshold level of PANA and PENA for triggering micturition and increased ATP and acetylcholine contents in the H 2O 2-treated bladder in the rat. Hyaluronic acid in vitro directly scavenged H 2O 2 in a dose-dependent manner. Intravesical hyaluronic acid for 30 min attenuated H 2O 2-elicited excitatory effects on the frequency of voiding, amplitude of IVP and the sensitization of PANA and PENA in the rats. Hyaluronic acid treatment reduced H 2O 2-induced ATP and acetylcholine release in the urinary bladder. Intravesical administration of muscarinic receptor antagonist atropine methyl nitrate (50 μM) or purinergic receptor antagonist PPADS (1mM) ameliorated H 2O 2-induced hyperactive bladder. Conclusions: These results indicate that hyaluronic acid treatment can ameliorate H 2O 2-induced bladder hyperactivity possibly via the antioxidant activity and the inhibition of activating purinergic and muscarinic signaling pathway.

Original languageEnglish
Pages (from-to)765-770
Number of pages6
JournalNeurourology and Urodynamics
Issue number5
Publication statusPublished - 2010 Jun
Externally publishedYes


  • ATP
  • Acetylcholine
  • Hyperactive bladder
  • Pelvic nerve
  • Reactive oxygen species

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology


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