Hyaluronic acid ameliorates bladder hyperactivity via the inhibition of H2O2-enhanced purinergic and muscarinic signaling in the rat.
OBJECTIVE
We hypothesize that increased H(2)O(2) in the urinary bladder may affect ATP and acetylcholine release and activate urothelial purinergic and muscarinic signaling consequently leading to hyperactive bladder.


METHODS
We infused 0.3% and 1.5% H(2)O(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(2)O(2) stimulation. Hyaluronic acid, muscarinic, and purinergic receptor antagonists were used to evaluate their effects and mechanisms on H(2)O(2)-induced hyperactive bladder.


RESULTS
Intravesical H(2)O(2) administration increased the frequency of voiding and the maximal amplitude of intravesical pressure (IVP) in the urethane anesthetized rats. Intravesical H(2)O(2) decreased the threshold level of PANA and PENA for triggering micturition and increased ATP and acetylcholine contents in the H(2)O(2)-treated bladder in the rat. Hyaluronic acid in vitro directly scavenged H(2)O(2) in a dose-dependent manner. Intravesical hyaluronic acid for 30 min attenuated H(2)O(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(2)O(2)-induced ATP and acetylcholine release in the urinary bladder. Intravesical administration of muscarinic receptor antagonist atropine methyl nitrate (50 microM) or purinergic receptor antagonist PPADS (1 mM) ameliorated H(2)O(2)-induced hyperactive bladder.


CONCLUSIONS
These results indicate that hyaluronic acid treatment can ameliorate H(2)O(2)-induced bladder hyperactivity possibly via the antioxidant activity and the inhibition of activating purinergic and muscarinic signaling pathway.
Yeh
Chung-Hsin
CH
Division of Urology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Chiang
Han-Sun
HS
Chien
Chiang-Ting
CT
D000818:Animals; D005260:Female; D006820:Hyaluronic Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D053201:Urinary Bladder, Overactive / Q000517:prevention & control*
D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D006820:Hyaluronic Acid; D006861:Hydrogen Peroxide