Mechanism of Action by Which Aspirin Alleviates Detrusor Hyperactivity in Rats

Tsukimi, Yasuhiro; Mizuyachi, Kaori; Matsumoto, Hiroko; Satô, Masako; Ng, Betty; Tajimi, Masaomi

doi:10.1254/jphs.95.101

Cited by 15 publications

(10 citation statements)

References 29 publications

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“…However, there are few reports describing the usefulness of aspirin in bladder disorders. Recently, we confirmed that aspirin was effective in overactive bladder in animal models (10). Therefore, in the present study, we examined the characteristics and the potential differences between aspirin and other NSAIDs such as indomethacin and ketoprofen.…”

Section: Discussionmentioning

confidence: 83%

“…Velasco et al (9) recently reported that aspirin increased bladder capacity in a model of overactive bladder in rats. Aspirin's efficacy in this model is most likely mediated by the inhibition of C-fiber activation as a consequence of PG synthesis blockade (10). In contrast to conventional NSAIDs, aspirin causes gastric damage only when given orally in rats (11).…”

Section: Introductionmentioning

confidence: 95%

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Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Takagi-Matsumoto

Tsukimi

et al. 2004

J Pharmacol Sci

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Abstract. To clarify the potential usefulness of non-steroidal anti-inflammatory drugs, NSAIDs, for patients with overactive bladder, we examined the effect of NSAIDs on urodynamic parameters in normal and cystitis rats and compared their ulcerogenic activity in the gastrointestinal mucosa. Cystometry was performed after administration of the conventional NSAIDs, aspirin, indomethacin, or ketoprofen. Prostaglandin levels were measured in the bladder of cystitis rats pretreated with NSAIDs. Furthermore, the ulcerogenic responses were examined. NSAIDs increased bladder capacity without any effect on micturition pressure in normal rats in the following rank order of potency: ketoprofen ³ indomethacin ³ aspirin. In cystitis rats, bladder capacity was increased and micturition frequency was decreased. The levels of prostaglandin were significantly increased in cystitis rats. All NSAIDs inhibited the increment of prostaglandin levels at doses equal to that effective in the improvement of bladder functions. When administered intraduodenally, both ketoprofen and indomethacin induced lesions in the gastrointestinal mucosa. However, aspirin had no significant effect. We demonstrate that NSAIDs are effective in animal models of disease, most likely by suppressing by prostaglandin synthesis. Since aspirin, in contrast to ketoprofen or indomethacin, did not cause any gastrointestinal lesions, aspirin might be the NSAIDs treatment of choice for overactive bladder.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 95%

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Takagi-Matsumoto

Tsukimi

et al. 2004

J Pharmacol Sci

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“…In addition, the urinary PGE 2 level has been reported to increase in patients with lower urinary tract obstruction (4). Previous studies have shown that NSAIDs decrease urinary frequency and increase bladder capacity in both normal and cystitis rats under urethane anesthesia (26,27). We also reported that loxoprofen inhibits enhancement of the micturition reflex after acetic acid-induced inflammation in conscious rats (24).…”

Section: Introductionmentioning

confidence: 62%

Synergistic effects of loxoprofen and glycine on the micturition reflex in consciousrats

et al. 2014

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We examined the inhibitory effects of loxoprofen, a cyclooxygenase inhibitor, and glycine, a major inhibitory neurotransmitter, on the micturition reflex in conscious rats and hypothesized that these drugs would interact synergistically to inhibit micturition. Voiding behaviors were assessed using a metabolic cage. Oral loxoprofen decreased the urinary frequency, and only a high dose (10 mg/kg) significantly reduced the voided volume. With cystometry, intravenous loxoprofen (0.1-3 mg/kg) and glycine (30 and 100 mg/kg) prolonged the intercontraction intervals (ICI) in a dose-dependent manner, but did not change the maximum voiding pressure (MVP) in conscious rats. The combination of loxoprofen (3 mg/kg) and glycine (100 mg/kg) strongly prolonged the ICI more than with either drug alone. The lowest dose of loxoprofen (0.1 mg/kg) and glycine (30 mg/kg) did not affect either the ICI or the MVP, but their combination resulted in a significant increase in the ICI. These results suggest that the combined administration of loxoprofen and glycine produced a synergistic inhibitory effect on the micturition reflex.Bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) induces various bladder dysfunctions. Nocturia in patients with BPH is one of the most bothersome symptoms of the disease. The presence of nocturia disrupts sleep, leading to daytime somnolence, depressive symptoms, cognitive dysfunction, and reduction in quality of life (10). Although nocturia in patients with BPH is commonly treated with α 1 -blockers and/or 5α-reductase inhibitors, using these drugs to reduce nocturia is not effective in many cases. Clinical reports have been published indicating that loxoprofen, a non-steroidal anti-inflammatory drug (NSAID), reduces not only pain and inflammation but also nocturia in patients with BPH (6,22).Other NSAIDs such as indomethacin also reduce the frequency of voiding and decrease the urine volume in patients with enuresis (1). NSAIDs including loxoprofen prevent prostaglandin (PG) synthesis by inhibiting the cyclooxygenase pathway. PGs, in particular PGE 2 , play an important role in regulating bladder function, and intravesical infusion of PGE 2 stimulates the micturition reflex by activating capsaicin-sensitive afferent nerves, leading to bladder overactivity in rats and humans (13,14,24). In addition, the urinary PGE 2 level has been reported to increase in patients with lower urinary tract obstruction (4). Previous studies have shown that NSAIDs decrease urinary frequency and increase bladder capacity in both normal and cystitis rats under urethane anesthesia (26,27). We also reported that loxoprofen inhibits enhancement of the micturition reflex after acetic acid-induced inflammation in conscious rats (24). However, the inhibitory effect of loxoprofen on the micturition reflex in normal, conscious states has not been fully examined. In addition, long-term use of NSAIDs is not recommended

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“…NVC was considered as spontaneous bladder contraction > 4mmHg from the baseline pressure that did not result in a void. The urodynamic variables evaluated and the methodology used in the CMGs match those described in the literature (17). Detrusor overactivity was defined as increase of NCV or MC.…”

Section: Cystometry In Anesthetized Ratsmentioning

confidence: 99%

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

et al. 2014

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ARTICLE INFO ______________________________________________________________ ______________________Purpose: The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Materials and Methods: Thirty-one male rats were randomized to following groups: 1 -control; 2 -L-Nitroarginine methyl ester (L-NAME); 3 -Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 -Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. Results:The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NA-ME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. Conclusion: In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

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Mechanism of Action by Which Aspirin Alleviates Detrusor Hyperactivity in Rats

Cited by 15 publications

References 29 publications

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Synergistic effects of loxoprofen and glycine on the micturition reflex in consciousrats

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

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