The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder

Mohammad S. Rahnama'i*, Gommert A. van Koeveringe, Philip E. V. A. Van Kerrebroeck, Stefan G. G. de Wachter

*Corresponding author for this work

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Abstract

Background: To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions. Methods: The urethra and bladder of 9 male guinea pigs (weight 270-300 g) were removed and placed in an organ bath with Krebs' solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE(2) were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled F-ini and P-ini, respectively. The steady state frequency (F-steady) and amplitude (P-steady) were defined as the average frequency and amplitude during the 5 minutes before the next wash out. Results: Application of 1 mu M PGE(2) increased the amplitude of spontaneous contractions without affecting frequency. 10 mu M of indomethacin reduced amplitude but not frequency. The addition of indomethacin did not alter F-ini after the first application (p = 0.7665). However, after the second wash, F-ini was decreased (p = 0.0005). F-steady, P-steady and P-ini were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE(2) addition. Conclusions: Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome.
Original languageEnglish
Article number8
JournalBMC Urology
Volume13
DOIs
Publication statusPublished - 7 Feb 2013

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