The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder
Koeveringe, van, Gommert A.
Kerrebroeck, van, Philip E.V.
Faculty of Medicine and Health Sciences
BMC urology. - London
, p. 1-9
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 270300 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. Results 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.. 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.