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Hyaluronic acid ameliorates bladder hyperactivity via the inhibition of H 2 O 2 ‐enhanced purinergic and muscarinic signaling in the rat
Author(s) -
Yeh ChungHsin,
Chiang HanSun,
Chien ChiangTing
Publication year - 2010
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20830
Subject(s) - purinergic receptor , muscarinic acetylcholine receptor , ppads , acetylcholine , endocrinology , urinary bladder , muscarinic acetylcholine receptor m3 , medicine , muscarinic antagonist , antagonist , atropine , carbachol , overactive bladder , chemistry , stimulation , receptor , pathology , alternative medicine
Aims 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. Materials and 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 µM) 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. Neurourol. Urodynam. 29:765–770, 2010. © 2010 Wiley‐Liss, Inc.