Mechanism of action by which aspirin alleviates detrusor hyperactivity in rats.
We examined the effect of aspirin on urodynamic parameters in normal and cyclophosphamide-induced cystitic rats and compared them in rats with or without sensory denervation. Cystometry was performed under urethane anesthesia; and volume threshold for micturition (VT), micturition frequency (MF), micturition pressure (MP), and micturition volume (MV) were determined. Cystitis was induced by pretreatment with cyclophosphamide and sensory denervation was performed by pretreating animals with a large dose of capsaicin. PGE(2) and 6-keto-PGF(1alpha) contents in the bladder were determined by ELISA. Sensory intact, cystitic rats showed decrement of VT and increment of MF. Aspirin increased VT and decreased MF in the cystitic condition. Both PGE(2) and 6-keto-PGF(1alpha) contents in the bladder were significantly increased in cystitic rats, but such increases were completely inhibited by aspirin. In sensory denervated rats, aspirin showed a marginal tendency of increment of VT. Cystitic rats showed overflow micturition in the sensory denervated condition, but VT was the same as that of normal rats. Furthermore, following capsaicin pretreatment, aspirin had no effect on the cystometrogram in cystitic rats. From these findings, it is concluded that suppression of sensory C-fiber via inhibition of PGs synthesis in the bladder is involved in the pharmacological action of aspirin in the detrusor hyperactivity.
Tsukimi
Yasuhiro
Y
TRA Urology, Laboratory-4, Research Center Kyoto, Bayer Yakuhin Ltd., Soraku-gun, Kyoto, Japan. Tsukimi_Yasuhiro@takeda.co.jp
Mizuyachi
Kaori
K
Matsumoto
Hiroko
H
Sato
Masako
M
Ng
Betty
B
Tajimi
Masaomi
M
D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D003556:Cystitis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D066298:In Vitro Techniques; D009122:Muscle Hypertonia / Q000188:drug therapy* / Q000503:physiopathology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001241:Aspirin