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

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 PGE2 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 Fini and Pini, respectively. The steady state frequency (Fsteady) and amplitude (Psteady) were defined as the average frequency and amplitude during the 5 minutes before the next wash out.Application of 1 μM PGE2 increased the amplitude of spontaneous contractions without affecting frequency. 10 μM of indomethacin reduced amplitude but not frequency.The addition of indomethacin did not alter Fini after the first application (p？=？0.7665). However, after the second wash, Fini was decreased (p？=？0.0005). Fsteady, Psteady and Pini were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE2 addition..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.The overactive bladder syndrome (OAB) is defined as urinary urgency with or without urgency incontinence, urinary frequency and nocturia. These symptoms still present a therapeutic challenge. Currently, antimuscarinic drugs are first-line treatment for OAB. How their beneficial action is achieved is still a matter of discussion. Depending on the studied compound, antimuscarinic drugs often have only moderate response rates when compared to placebo [1]. However, adverse effects